大肠高危腺瘤和癌变息肉的临床分析及decorin在腺瘤中的表达与意义
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摘要
目的研究大肠息肉癌变过程中的相关因素,探讨大肠高危腺瘤及癌变息肉的临床及内镜病理特征,为合理的结肠镜检查随访提供依据。并研究decorin在大肠腺瘤中的表达情况,探讨decorin与息肉恶变倾向的关系。
方法选择安徽医科大学第一附属医院消化科2005-2008年间肠镜下切除并经病理证实符合诊断标准的大肠息肉患者583例(部分来自普外科手术病例)。采用统一设计的个案登记表格,详细记录其临床病理信息,对获得的资料进行整理归纳,按照2006年美国《大肠息肉切除术后随访指南》将大肠息肉患者进行风险分层,即分为低危腺瘤、高危腺瘤及非腺瘤性息肉组,采用回顾性分析的方法对三组和癌变息肉进行临床病理分析。同时,从上述病例中选取我院病理科完整存档蜡块86例包括炎性和增生性息肉病例16例,腺瘤70例进行免疫组化S-P法染色,检测decorin在大肠息肉组织中的表达情况。另选取手术病理证实的大肠癌标本18例,正常大肠黏膜标本20例作为对照观察。
结果1.大肠高危腺瘤及癌变息肉的临床分析583例大结肠息肉患者中,非腺瘤性息肉243例,低危腺瘤83例,高危腺瘤257例。腺瘤性息肉组平均年龄58.90±13.28岁,高于非腺瘤性息肉组55.51±15.66岁(P<0.05)；腺瘤性息肉组中其息肉直径≥1cm及数目≥3个者均高于非腺瘤性息肉组(分别为62.0%Vs21.5%,24.1%Vs14.0%,P均<0.01)；腺瘤性息肉癌变率为9.1%,非腺瘤性息肉是0.8%(P<0.001)。高危腺瘤组较低危腺瘤组其便血症状增多(51.8%Vs37.3%,P<0.05),在内镜下更易观察到黏膜改变和表面分叶情况(P<0.05)。本组33例大肠息肉发生癌变,其中息肉直径≥2.0cm的和数目≥3个的息肉癌变率分别为21.1%和11.2%,均显著高于息肉直径≥1.Ocm者(4.2%,P<0.001)和数目<3个者(4.3%,P<0.05)；表面分叶的息肉癌变率为19.3%,高于无表面分叶的息肉癌变率(2.2%,P<0.001)；息肉癌变在绒毛状腺瘤为26.8%,绒毛管状腺瘤为21.1%,管状腺瘤2.3%,绒毛状腺瘤和管状绒毛状腺瘤的癌变率均显著高于管状腺瘤(P均<0.001)。
2.Decorin在大肠腺瘤中的表达Decorin在正常组织和非腺瘤性息肉以及管状腺瘤组织中呈高表达(高表达率分别为90.0%,87.5%,84.4%),均高于含绒毛状结构腺瘤(63.2%)和大肠癌组织(44.4%)(P均<0.05)；decorin在伴低级别上皮内瘤变的腺瘤中高表达率为92.0%,显著高于伴高级别上皮内瘤变的腺瘤(53.3%)(P<0.05)；在6例癌变腺瘤中,decorin的高表达率仅为33.3%,显著低于无癌变的腺瘤76.6%(P<0.05)。Decorin的表达与腺瘤的含绒毛状结构与异型增生程度相关。
结论高危腺瘤较低危腺瘤其便血症状增多,在内镜下更易观察到黏膜改变和表面分叶等形态学改变,具备高危因素如腺瘤体积越大、数目越多、含绒毛成分多及呈分叶或菜花状者越易发生癌变；Decorin的表达与腺瘤的含绒毛状结构与异型增生程度相关,decorin蛋白的检测可能是一种有价值的指标用于息肉恶性程度的评价。
Objective Give a research to the canceration factors for colorectal polyps and to investigate the endoscopic and pathologic characteristics of colorectal high-risk adenomas for a reasonable follow-up colonoscopy. To investigate the expression of decorin in colorectal adenomas,otherwise to analyze the relationship of the expression with clinicopathologic and risk factors.
Methods 583 colon polyp patients who underwent colonoscopic resection between 2005 and 2008 at the department of gastroenterology,the first affiliated hospital of anhui medical university (some cases underwent surgical resection)were analyzed retrospective. According to the 2006 postpolypectomy colonoscopy surveillance guideline,583cases with colonic polyps were stratified at their baseline into lower risk group,increased risk group and non-adenomatous polyps group,moreover,undertook statistical treatment to related clinical parameter.Immunohistochemical methods(S-P) were used to detect decorin protein in 16 inflammatory or hyperplastic polyps and 70 colorectal adenomas paraffinembedded tissue specimens,18 colon cancer and 86 colon polyps tissue as control groups.
Results 1.Clinical analysis of colorectal advanced adenomas The number of patients with colonic polyps was 583, including 243 non-adenomatous polyps,83 low-risk adenomas,257 high-risk adenomas. The average age of adenomatous polyps patients was older than that of the non-adenomatous polyps patients(58.90±13.28 vs 55.51±15.66,P<0.05);Compared with non-adenomatous polyposis, adenomatous polyposis is significantly diferent in size and number of polyps, adenomatous polyps Patients whose polyps≥lcm and≥3adenomas was more than non-adenomatouss polyps patients (62.0%Vs21.5%,24.1%Vs14.0%,P<0.01,respectively),and there was a significant difference the incidence in cancerous polyps than in non-adenomatous polyps patients (9.1%vs0.8%, P<0.001).The high-risk adenomas has higher incidence of hematochezia (51.8%Vs37.3%,P<0.05),more lobular and mucosal pathological change than low-risk adenomas.33 cases were cancerated in our study, in which, canceration rate of polyps≥2.0cm in diameter and the number of polyps≥3were 21.1% and 11.2%, were significantly higher than those polyps≥1.0cm in diameter (4.2%, P＜0.001) and the number of<3 (4.3%, P<0.05); there was a higher canceration rate for the polyps with Surface lobulation(19.3%),than their with non-Surface lobulation(2.2%)(P＜0.001);The canceration rate of villous adenoma(26.8%) and tubular-villous adenoma (21.1%)was higher than tubular adenoma (2.3%) (P＜0.001, respectively).2.Expression of decorin in colon polyps Normal tissue and non-adenomatous polyps and the majority of tubular adenomas showed strong expression of decorin in the stroma(high expression rates were 90.0%,87.5%,84.4%, respectively),adenomas with villous features and the high grade colon intraepithelial neoplasia and adenocarcinoma showed moderate and very low decorin immunoreactivity(high expression rates were 63.2%,53.3%%,44.4%) (P<0.05, respectively);In the 6 cases of malignant adenomas, high decorin expression rate was only 33.3%, significantly lower than non-cancerous adenomas 76.6%(P<0.05).Decorin expression levels were significantly related to histological features and dysplasia grade of adenomas.
Conclusion The high-risk adenomas has higher incidence of hematochezia,more lo-bular and mucosal pathological change than low-risk adenomas. The totality of evidence suggests that multiplicity, size, villous features, and more lobular and mucosal path-ological change are predictors of future advanced adenomas or cancers;The test of expression of decorin protein is helpful in assessing the malignant extent of colorectal polyps
方法选择安徽医科大学第一附属医院消化科2005-2008年间肠镜下切除并经病理证实符合诊断标准的大肠息肉患者583例(部分来自普外科手术病例)。采用统一设计的个案登记表格,详细记录其临床病理信息,对获得的资料进行整理归纳,按照2006年美国《大肠息肉切除术后随访指南》将大肠息肉患者进行风险分层,即分为低危腺瘤、高危腺瘤及非腺瘤性息肉组,采用回顾性分析的方法对三组和癌变息肉进行临床病理分析。同时,从上述病例中选取我院病理科完整存档蜡块86例包括炎性和增生性息肉病例16例,腺瘤70例进行免疫组化S-P法染色,检测decorin在大肠息肉组织中的表达情况。另选取手术病理证实的大肠癌标本18例,正常大肠黏膜标本20例作为对照观察。
结果1.大肠高危腺瘤及癌变息肉的临床分析583例大结肠息肉患者中,非腺瘤性息肉243例,低危腺瘤83例,高危腺瘤257例。腺瘤性息肉组平均年龄58.90±13.28岁,高于非腺瘤性息肉组55.51±15.66岁(P<0.05)；腺瘤性息肉组中其息肉直径≥1cm及数目≥3个者均高于非腺瘤性息肉组(分别为62.0%Vs21.5%,24.1%Vs14.0%,P均<0.01)；腺瘤性息肉癌变率为9.1%,非腺瘤性息肉是0.8%(P<0.001)。高危腺瘤组较低危腺瘤组其便血症状增多(51.8%Vs37.3%,P<0.05),在内镜下更易观察到黏膜改变和表面分叶情况(P<0.05)。本组33例大肠息肉发生癌变,其中息肉直径≥2.0cm的和数目≥3个的息肉癌变率分别为21.1%和11.2%,均显著高于息肉直径≥1.Ocm者(4.2%,P<0.001)和数目<3个者(4.3%,P<0.05)；表面分叶的息肉癌变率为19.3%,高于无表面分叶的息肉癌变率(2.2%,P<0.001)；息肉癌变在绒毛状腺瘤为26.8%,绒毛管状腺瘤为21.1%,管状腺瘤2.3%,绒毛状腺瘤和管状绒毛状腺瘤的癌变率均显著高于管状腺瘤(P均<0.001)。
2.Decorin在大肠腺瘤中的表达Decorin在正常组织和非腺瘤性息肉以及管状腺瘤组织中呈高表达(高表达率分别为90.0%,87.5%,84.4%),均高于含绒毛状结构腺瘤(63.2%)和大肠癌组织(44.4%)(P均<0.05)；decorin在伴低级别上皮内瘤变的腺瘤中高表达率为92.0%,显著高于伴高级别上皮内瘤变的腺瘤(53.3%)(P<0.05)；在6例癌变腺瘤中,decorin的高表达率仅为33.3%,显著低于无癌变的腺瘤76.6%(P<0.05)。Decorin的表达与腺瘤的含绒毛状结构与异型增生程度相关。
结论高危腺瘤较低危腺瘤其便血症状增多,在内镜下更易观察到黏膜改变和表面分叶等形态学改变,具备高危因素如腺瘤体积越大、数目越多、含绒毛成分多及呈分叶或菜花状者越易发生癌变；Decorin的表达与腺瘤的含绒毛状结构与异型增生程度相关,decorin蛋白的检测可能是一种有价值的指标用于息肉恶性程度的评价。
Objective Give a research to the canceration factors for colorectal polyps and to investigate the endoscopic and pathologic characteristics of colorectal high-risk adenomas for a reasonable follow-up colonoscopy. To investigate the expression of decorin in colorectal adenomas,otherwise to analyze the relationship of the expression with clinicopathologic and risk factors.
Methods 583 colon polyp patients who underwent colonoscopic resection between 2005 and 2008 at the department of gastroenterology,the first affiliated hospital of anhui medical university (some cases underwent surgical resection)were analyzed retrospective. According to the 2006 postpolypectomy colonoscopy surveillance guideline,583cases with colonic polyps were stratified at their baseline into lower risk group,increased risk group and non-adenomatous polyps group,moreover,undertook statistical treatment to related clinical parameter.Immunohistochemical methods(S-P) were used to detect decorin protein in 16 inflammatory or hyperplastic polyps and 70 colorectal adenomas paraffinembedded tissue specimens,18 colon cancer and 86 colon polyps tissue as control groups.
Results 1.Clinical analysis of colorectal advanced adenomas The number of patients with colonic polyps was 583, including 243 non-adenomatous polyps,83 low-risk adenomas,257 high-risk adenomas. The average age of adenomatous polyps patients was older than that of the non-adenomatous polyps patients(58.90±13.28 vs 55.51±15.66,P<0.05);Compared with non-adenomatous polyposis, adenomatous polyposis is significantly diferent in size and number of polyps, adenomatous polyps Patients whose polyps≥lcm and≥3adenomas was more than non-adenomatouss polyps patients (62.0%Vs21.5%,24.1%Vs14.0%,P<0.01,respectively),and there was a significant difference the incidence in cancerous polyps than in non-adenomatous polyps patients (9.1%vs0.8%, P<0.001).The high-risk adenomas has higher incidence of hematochezia (51.8%Vs37.3%,P<0.05),more lobular and mucosal pathological change than low-risk adenomas.33 cases were cancerated in our study, in which, canceration rate of polyps≥2.0cm in diameter and the number of polyps≥3were 21.1% and 11.2%, were significantly higher than those polyps≥1.0cm in diameter (4.2%, P＜0.001) and the number of<3 (4.3%, P<0.05); there was a higher canceration rate for the polyps with Surface lobulation(19.3%),than their with non-Surface lobulation(2.2%)(P＜0.001);The canceration rate of villous adenoma(26.8%) and tubular-villous adenoma (21.1%)was higher than tubular adenoma (2.3%) (P＜0.001, respectively).2.Expression of decorin in colon polyps Normal tissue and non-adenomatous polyps and the majority of tubular adenomas showed strong expression of decorin in the stroma(high expression rates were 90.0%,87.5%,84.4%, respectively),adenomas with villous features and the high grade colon intraepithelial neoplasia and adenocarcinoma showed moderate and very low decorin immunoreactivity(high expression rates were 63.2%,53.3%%,44.4%) (P<0.05, respectively);In the 6 cases of malignant adenomas, high decorin expression rate was only 33.3%, significantly lower than non-cancerous adenomas 76.6%(P<0.05).Decorin expression levels were significantly related to histological features and dysplasia grade of adenomas.
Conclusion The high-risk adenomas has higher incidence of hematochezia,more lo-bular and mucosal pathological change than low-risk adenomas. The totality of evidence suggests that multiplicity, size, villous features, and more lobular and mucosal path-ological change are predictors of future advanced adenomas or cancers;The test of expression of decorin protein is helpful in assessing the malignant extent of colorectal polyps
引文
1. Winawer SJ,Zauber AG,Fletcher RH,et al. Guidelines for colonoscopy surveillance after polypectomy:A consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. Gastroenterology,2006, 130:1872-1885.
2. Lieberman DA,Weiss DG, Harford WV, et al. Five-year colon surveillance after screening colonoscopy. Gastroenterology,2007,133:1077-1085.
3. Imperiale TF,Sox HC.Guidelines for surveillance intervals after polypectomy: coping with the evidence.Ann Intern Med,2008,148:477-479.
4. Gupta S.Colorectal Polyps:The Scope and Management of the Problem.Am J Med Sci,2008,336:407-417.
5. Sheikh RA,Min BH, Yasmeen S,et al.Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas.Dig Dis Sci,2003,48:223-229.
6. Goldoni S,Iozzo RV.Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs.Int J Cancer,2008,123:2473-2479.
7. Seidler DG, Schaefer L, Robenek H, et al. A physiologic three-dimensional cell culture svstem to investigate the role of decorin in matrix organization and cell survival. Biochem Biophys Res Commun,2005,332:1162-1170.
8. Daniela G. Seidler,Silvia Goldoni,Christopher Agnew,et al. Decorin protein core inhibits in vivo cancer growth and metabolism by hindering epidermal growth factor receptor function and triggering apoptosis via caspase-3 activation. J Biol Chem,2006,281:26408-26418.
9. Moscatello DK, Santra M, Mann DM, et al:Decorin suppresses tumor cell growth by activating the epidermal growth factor receptor. J Clin Ivest,1998,101:406-412.
10. Stander M,Naumann U,Dumitrescu L, et al.Decorin gene transfer-mediated suppression of TGF beta synthesis abrogates experimental malignant glioma growth in vivo.Gene Ther,1998,5:1187-1194.
11. Sandra Troup,Catherine Njue, Erich V. Kliewer, et al.Reduced Expression of the Small Leucine-rich Proteoglycans,Lumican, and Decorin Is Associated with Poor Outcome in Node-negative Invasive Breast Cancer. Clin Cancer Res,2003, 9:206-214.
12. Salomaki HH,Sainio AO,Soderstrom M,et al. Differential expression of decorin by human malignant and benign vascular tumors. J Histochem Cytochem,2008, 56:639-646.
13. Arnaldi LA, Borra RC, Maciel RM,et al.Gene expression profiles reveal that DCN, DIO1, and DIO2 are underexpressed in benign and malignant thyroid tumors.Thyroid,2005,15:210-221.
14. Akihiko Matsumine,Ken Shintani,Katsuyuki Kusuzaki,et al.Expression of Decorin, a Small Leucine-Rich Proteoglycan, as a Prognostic Factor in Soft Tissue Tumors.J Surg Oncol,2007,96:411-418.
15. Santra M, Skorski T, Calabretta B,et al.De novo decorin gene expression suppresses the malignant phenotype in human colon cancer cells.Proc Natl Acad Sci U S A. 1995,92:7016-7020.
16. Augoff K,Rabczynski J,Tabola R,et al.Immunohistochemical study of decorin expression in polyps and carcinomas of the colon.Med Sci Monit,2008,14:530-535.
17. Bi X,Tong C, Dockendorff A,et al. Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation.Carcinogenesis, 2008,29:1435-1440.
18.全国大肠癌病理研究组.全国大肠癌病理研究统一规范.全国大肠癌病理读片会,杭州,1982,12-16.
19. V T Labropoulou,A D Theocharis,1 P Ravazoula,et al.Versican but not decorin accumulation is related to metastatic potential and neovascularization in testicular germ cell tumours.Histopathology,2006,49:582-593.
20. Giacosa A,Frascio F,Munizzi F.Epidemiology of colorectalpolyps.Tech Coloproctol, 2004,8(Suppl2),a243.
21.李伏娥,叶红军,李坚等.796例大肠息肉的临床、内镜及病理观察.中南大学学报(医学版),2005,30：463.
22. Bond JH.Colon polyps and cancer.Endoscopy,2005,37:208.
23.郏芝田.胃肠病学.第3版.北京：人民卫生出版社,2000：846.
24. Sanderson SJ, Ewing Sk, Wiehr CL, et al. Aberrant expression of MUC5AC and MUC6 gastric mucin genes in colorectal polyps.InI J Cancer,1999,80:210-218.
25.黄超,黄梅芳,朱尤庆.大肠息肉946例临床分析.实用医学杂志,2005,18：2048-2049.
26.王永华,卢忠生,王向东.不同病理类型结直肠息肉的差别.胃肠病学和肝病学杂志,2003,12：563-565.
27. Lieberman DA,W eiss DG. Five year surveillance of patients with adenomas or colorectal cancer at screening colonoscopy (results from the VA Cooperative Study#380).Gastroenterology,2004,126:A22.
28.Noshirwani KC,van Stolk RU,Rybicki LA,et al. Adenoma size and number are predictive of adenoma recurrence(implications for surveillance colonoscopy). Gastrointest Endosc,2000,51:433-437.
29.陈灏珠.实用内科学.第12版.北京：人民卫生出版社,2005：1934.
30. Lieberman DA.Targted colon cancer screening a concept whose time has almost come.Am J Gastroenterol,1992,87:1085-1093.
31.梅俏,鲍峻峻,许建明,等.228例大肠高危腺瘤性息肉的回顾性分析[J].安徽医学,2008,29：392-394.
32. Yang G,Zheng W,Sun QR,et al.Pathologic features of initial adenomas as predictors for metachronous adenomas of the rectum.J Natl Cancer Inst,1998,90:1661-1665.
33. Bertario L, Russo A, Sala P,et al. Predictors of metachronous colorectal neoplasms in sporadic adenoma patients. Int J Cancer 2003,105:82-87.
34.欧希龙,孙为豪,曹大中,等.大肠息肉及恶性肿瘤活检与整体病理诊断差异性分析.中华消化内镜杂志,2004,21：277-279.
35. Sung SY,Hsieh CL, Wu D,et al.Tumor microenvironment promotes cancer progression,metastasis,and therapeutic resistance.Curr Probl Cancer.2007,31: 36-100.
36. Schaefer L, Iozzo RV.Biological functions of the small leucine-rich proteoglycans: from genetics to signal transduction.J Biol Chem.2008,283:21305-21309.
37. Wegrowski Y,Maquart FX.Involvement of stromal proteoglycans in tumour progression.Crit Rev Oncol Hematol.2004,49:259-268.
38. Iozzo RV.The family of the small leucine-rich proteoglycans:key regulators of matrix assembly and cellular growth.Crit Rev Biochem Mol Biol.1997,32:141-174.
39. De Luca A,Santra M, Baldi A,et al. Decorin-induced growth suppression is associated with up-regulation of p21, an inhibitor of cyclin-dependent kinases. J Biol Chem.1996,271:18961-18965.
40. Iozzo RV,Moscatello DK, McQuillan DJ,et al.Decorin is a biological ligand for the epidermal growth factor receptor. J Biol Chem 1999,274:4489-4492.
41. Moscatello DK, Santra M,Mann DM,et al.Decorin suppresses tumor cell growth by activating the epidermal growth factor receptor. J Clin Invest.1998,101:406-412.
42. Derynck R,Akhurst RJ,Balmain A.TGF-beta signaling in tumor suppression and cancer progression. Nat Genet.2001,29:117-129.
43. Davies Cde L,Melder RJ,Munn LL, et al.Decorin inhibits endothelial migration and tube-like structure formation: Role of thrombospondin-1. Microvasc Res. 2001,62:26-42.
44. Silvia Goldoni,Ashley Humphries,Alexander Nystrom,et al.Decorin is a novel antagonistic ligand of the Met receptor.J Cell Biol,2009,185:743-754.
45. Grant DS,Yenisey C, Rose RW, et al.Decorin suppresses tumor cell-mediated angiogenesis. Oncogene,2002,21:4765-4777.
46. Petit AMV, Rak J,Hung M-C,et al. Neutralizing antibodies against epidermal growth factor and Erb-2/neu receptor tyrosine kinases down-regulated vascular endothelial growth factor production by tumor cells in vitro and in vivo.Angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol. 1997,151:1523-1530.
47.赵素莲,王桂琴,田树华,等.Decorin对肝癌细胞株凋亡作用的研究.肿瘤防治杂志,2002,9：235-237.
48. Biglari A,Bataille D,Naumann U, et al.Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model. Cancer Gene Ther. 2004,11:721-732.
49. Nash MA,Deavers MT, Freedman RS.The expression of decorin in human ovarian tumors.Clin Cancer Res.2002,8:1754-1760.
50. Tralhao JG,Schaefer L,Micegova M,et al.In viva selective and distant killing of cancer cells using adenovirus-mediated decorin gene transfer.FASEB J,2003,17:464-466.
51.Kentaro Araki,Hiroki Wakabayashi,Ken Shintani,et al.Decorin Suppresses Bone Metastasis in a Breast Cancer Cell Line.Oncology,2009,77:92-99.
52. Koninger J,Giese NA, di Mola FF, et al. Overexpressed decorin in pancreatic cancer: potential tumor growth inhibition and attenuation of chemotherapeutic action. Clin Cancer Res,2004,10:4776-4783.
53.戎彪学,蔡曦光,马慧,等Decorin mRNA和p57 mRNA在非小细胞肺癌中的表达及其临床意义.临床肿瘤学杂志,2006,11：331-335.
54.傅锦业,吴毅,王卓颖,等Decorin在甲状腺恶性肿瘤中的表达及其临床意义. 中华内分泌代谢杂志.2008,24：68-69.
55. Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med.1992,326:658-662.
56.朱雄增.学习和掌握肿瘤的WHO分类,提高病理诊断和研究的水平.中华病理学杂志,2006,35：649.
57. Laiyemo AO,Murphy G, Albert PS, et al.Postpolypectomy colonoscopy surve-illance guidelines:predictive accuracy for advanced adenoma at 4 years.Ann Intern Med.2008,148:419-426.
1. Sung SY,Hsieh CL, Wu D,et al.Tumor microenvironment promotes cancer progression,metastasis,and therapeutic resistance.Curr Probl Cancer.2007, 31:36-100.
2. lozzo RV.The family of the small leucine-rich proteoglycans:key regulators of matrix assembly and cellular growth.Crit Rev Biochem Mol Biol.1997,32:141-174.
3. Wegrowski Y,Maquart FX.Involvement of stromal proteoglycans in tumour progression.Crit Rev Oncol Hematol.2004,49:259-268.
4. Schaefer L, lozzo RV. Biological functions of the small leucine-rich proteoglycans: from genetics to signal transduction. J Biol Chem.2008,283:21305-21309.
5. lozzo RV.The biology of the small leuclne-rich proteoglycans functional network of interactive proteins. J Biol Chem,1999,274:18843-18846.
6. Goldoni S,Iozzo RV.Tumor microenvironment:Modulation by decorin and related molecules harboring leucine-rich tandem motifs.Int J Cancer,2008,123:2473-2479.
7. Kresse H,Schonherr E.Proteoglycans the extracellular matrix and growth control.J Cell Physiol,2001,189:266-274.
8. Bi Y, Stueltens CH, Kilts T, et al.Extracellular matrix proteoglycans control the fate of bone marrow stromal cells. J Biol Chem.2005,280:30481-30489.
9. Jarvelainen H, Puolakkainen P, Pakkanen S, et al.. A role for decorin in cutaneous wound healing and angiogenesis. Wound Repair Regen 2006; 14:443-452.
10. Seidler DG, Schaefer L, Robenek H, et al. A physiologic three-dimensional cell culture svstem to investigate the role of decorin in matrix organization and cell survival. Biochem Biophys Res Commun,2005,332:1162-1170.
11. Akihiko Matsumine,Ken Shintani,Katsuyuki Kusuzaki,et al.Expression of Decorin, a Small Leucine-Rich Proteoglycan, as a Prognostic Factor in Soft Tissue Tumors.J Surg Oncol,2007,96:411-418.
12. Sandra Troup, Catherine Njue, Erich V. Kliewer, et al. Reduced Expression of the Small Leucine-rich Proteoglycans,Lumican, and Decorin Is Associated with Poor Outcome in Node-negative Invasive Breast Cancer. Clin Cancer Res,2003, 9:206-214.
13..Iozzo RV,Moscatello DK, McQuillan DJ,et al.Decorin is a biological ligand for the epidermal growth factor receptor. J Biol Chem 1999,274:4489-4492.
14. Moscatello DK, Santra M,Mann DM,et al.Decorin suppresses tumor cell growth by activating the epidermal growth factor receptor. J Clin Invest.1998,101:406-412.
15. Csordas G, Santra M, Reed CC, et al.Sustained down-regulation of the epidermal growth factor receptor by decorin. A mechanism for controlling tumor growth in vivo. J Biol Chem,2000,275:32879-32887.
16. De Luca A,Santra M, Baldi A,et al. Decorin-induced growth suppression is associated with up-regulation of p21, an inhibitor of cyclin-dependent kinases. J Biol Chem.1996,271:18961-18965.
17. Schonherr E, Levkau B, Schaefer L,et al.Decorin-mediated signal transduction in endothelial cells. Involvement of Akt/protein kinase B in up-regulation of p21(WAF1/CIP1) but not p27(KIP1).J Biol Chem.2001,276:40687-40692.
18. Reed CC,Gauldie J,Iozzo RV.Suppression of tumorigenicity by Adenovirus-mediated gene transfer of decorin.Oncogene,2002,21:3688-3695.
19. Csordas G,Santra M,Reed CC,et al.Sustained down-regulation of the epidermal growth factor receptor by decorin:A mechanism for controlling tumor growth in vivo.J Biol Chem,2000,275:32879-32887.
20. Daniela G. Seidler, Silvia Goldoni, Christopher Agnew,et al. Decorin protein core inhibits in vivo cancer growth and metabolism by hindering epidermal growth factor receptor function and triggering apoptosis via caspase-3 activation. J Biol Chem,2006,281:26408-26418.
21.Schonherr E, Sunderkotter C, Iozzo RV, et al. Decorin, a novel player in the insulin-like growth factor system. J Biol Chem,2005,280:15767-15772.
22. Schaefer L, Tsalastra W, Babelova A, et al. Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-1 receptor and mammalian target of rapamycin. Am J Pathol,2007,170:301-315.
23. Schonherr E, Bodo Levkau, Schaefer L,et al.Decorin-mediated Signal Transduction in Endothelial Cells.J Biol Chem,2001,276:40687-40692.
24. Stella MC, Trusolino L,Pennacehietti S, et al. Negative feedback regulation of met-dependent invasive growt h by notch. Mol Cell Biol,2005,25:3982-3996.
25. Silvia Goldoni, Ashley Humphries, Alexander Nystrom,et al.Decorin is a novel antagonistic ligand of the Met receptor.J Cell Biol,2009,185:743-754.
26. Enrique Brandanl, Claudio Retamal, Claudio Cabello-Verrugio,et al.The Low Density Lipoprotein Receptor-related Protein Functions as an Endocytic Receptor for Decorin. J Biol Chem,2006,281:31562-31571.
27. Claudio Cabello-Verrugiol.Enrique Brandan.A novel modulatory mechanism of transforming growth factor-b signaling through decorin and LRP-1.J Biol Chem, 2007,282:18842-18845.
28. Derynck R,Akhurst RJ,Balmain A.TGF-beta signaling in tumor suppression and cancer progression. Nat Genet.2001,29:117-129.
29. Marko S,Ulrike N,Wolfgang W,et al.Transforming growth factorβand p-21:multiple molecular targets of decorin-mediated suppression of euplastic growdth.J Cell rrisstte Res.1999,296:221.
30. Davies Cde L,Melder RJ,Munn LL, et al.Decorin inhibits endothelial migration and tube-like structure formation:Role of thrombospondin-1. Micro vasc Res.2001, 62:26-42.
31.tander M,Naumann U,Dumitrescu L, et al.Decorin gene transfer-mediated suppression of TGF beta synthesis abrogates experimental malignant glioma growth in vivo.Gene Ther,1998,5:1187-1194.
32. Xiuli Bi, Tong C, Dokendorff A, et al. Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis,2008,29:1435-1440.
33. Grant DS, Yenisey C, Rose RW, et al.Decorin suppresses tumor cell-mediated angiogenesis. Oncogene,2002,21:4765-4777.
34. Petit AMV, Rak J, Hung M-C, et al.Neutralizing antibodies against epidermal growth factor and Erb-2/neu receptor tyrosine kinases down-regulated vascular endothelial growth factor production by tumor cells in vitro and in vivo. Angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 1997;151:1523-1530.
35. Salomaki HH, Sainio AO, Soderstrom M, et al. Differential expression of decorin by human malignant and benign vascular tumors. J Histochem Cytochem, 2008,56:639-646.
36.赵素莲,王桂琴,田树华,等.Decorin对肝癌细胞株凋亡作用的研究.肿瘤防治杂志,2002,3：235-237.
37. Jorg Koninger,Nathalia A. Giese,Fabio Francesco di Mola, et al.Overexpressed Decorin in Pancreatic Cancer:Potential Tumor Growth Inhibition and Attenuation of Chemotherapeutic Action.Clin Cancer Res.2004,10:4776-4783.
38. Theocharis AD, Vynios DH, Papageorgakopoulou N, et al.Altered content composition and structure of glycosaminoglycans and proteoglycans in gastric carcinoma. Int J Biochem Cell Biol.2003;35:376-390.
39. Miyasaka Y, Enomoto N, Nagayama K, et al.Analysis of differentially expressed genes in human hepatocellular carcinoma using suppression subtractive hybridization. Br J Cancer.2001;85:228-234.
40. McDoniels-Silvers AL, Nimri CF, Stoner GD, et al. Differential gene expression in human lung adenocarcinomas and squamous cell carcinomas. Clin Cancer Res 2002;8:1127-1138.
41.Leygue E, Snell L, Dotzlaw H, et al.Lumican and decorin are differentially expressed in human breast carcinoma. J Pathol.2000;192:313-320.
42. Reed CC, Waterhouse A, Kirby S, et al.Decorin prevents metastatic spreading of breast cancer. Oncogene 2005;24:1104-1110.
43. Michael A. Nash, Michael T. Deavers, Ralph S. Freedmanl.The Expression of Decorin in Human Ovarian Tumors.Clin Cancer Res.2002,8:1754-1760.
44. Grisaru D, Hauspy J, Prasad M, et al.Microarray expression identification of differentially expressed genes in serous epithelial ovarian cancer compared with bulk normal ovarian tissue and ovarian surface scrapings.Oncol Rep, 2007,18:1347-1356.
45. Arnaldi LA, Borra RC, Maciel RM,et al.Gene Expression Profiles Reveal that DCN, DIO1,and DIO2 Are Underexpressed in Benign and Malignant Thyroid Tumors.Thyroid.2005,15:210-221.
46.傅锦业, 吴毅, 王卓颖.伴颈部淋巴结转移的甲状腺乳头状癌的基因差异表达.中国癌症杂志,2006,16：980-984.
47. Adany R, Heimer R, Caterson B, et al. Altered expression of chondroitin sulfate proteoglycan in the stroma of human colon carcinoma.Hypomethlation of PG-40 gene correlates with increased PG-40 content and mRNA levels. J Biol Chem, 1990,265:11389-11396.
48. Augoff K, Rabczynski J, Tabola R,et al.Immunohistochemical study of decorin expression in polyps and carcinomas of the colon.Med Sci Monit,2008,14:530-535.
49. Santra M, Skorski T, Calabretta B,et al. De novo decorin gene expression suppresses the malignant phenotype in human colon cancer cells. Proc Natl Acad Sci USA 1995,92:7016-7020.
50. Biglari A, Bataille D, Naumann U, et al. Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model. Cancer Gene Ther, 2004,11:721-732.
51. Pan S, Cheng L, White JT, et al.Quantitative proteomics analysis integrated with microarray data reveals that extracellular matrix proteins, catenins, and p53 binding protein 1 are important for chemotherapy response in ovarian cancers.OMICS. 2009,13:345-354.
52. Goldoni S,Iozzo RV.Tumor microenvironment:Modulation by decorin and related molecules harboring leucine-rich tandem motifs.Int J Cancer,2008,123:2473-2479.
53.操海萍,舒振波,王维忠,等.核心蛋白聚糖在乳腺癌中表达的探讨.中国肿瘤临床,2006,33：1105-1108.
54.戎彪学,蔡曦光,马慧,等Decorin mRNA和p57 mRNA在非小细胞肺癌中的表达及其临床意义.临床肿瘤学杂志,2006,11：331-335.
55.傅锦业,吴毅,王卓颖,等Decorin在甲状腺恶性肿瘤中的表达及其临床意义.中华内分泌代谢杂志,2008,24：68-69.
56. Crnogorae-Jurcevic T,Efthimiou E,Capelli P,et al.Gene expression profiles of pancreatic cancer and stromal desmoplasia.Oneogene,2001,20:7437-7446.
57. Skandalis SS, Theocharis AD, Theocharis DA, et. Al.Matrix proteoglycans are markedly affected in advanced laryngeal squamous cell carcinoma. Biochem Biophys Acta 2004;1689:152-161.
58. Brown LF, Guidi AJ, Schnitt SJ, et al. Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast. Clin Cancer Res 1999;5:1041-1056.
59. Koninger J, Giese T, di Mola FF,et,al. Pancreatic tumor cells influence the composition of the extracellular matrix. Biochem Biophys Res Commun, 2004,322:943-949.
60. Merle B, Durussel L, Delmas PD, et al. Decorin inhibits cell migration through a process requiring its glycosaminoglycan side chain. J Cell Biochem, 1999,75：538-546.
61.张玉成,王雅丽,杜珍武,等.核心蛋白聚糖在HepG_2细胞中的表达与作用.山东医药,2008,7：35-37.
62.赵斌燕,齐峰Decorin因子对人胃癌细胞及其表达的MG7蛋白的作用.中华医学研究杂志,2006,1：19-20.
63. Santra M, Skorski T, Calabretta B, et al. De novo deeorin gene expression suppresses the malignant phenotype in human colon cancer cells. Proc Natl Acad Sci U S A,1995,92:7016-7020.
64. Nash MA, Loercher AE, Freedman RS. In vitro growth inhibition of ovarian cancer cells by decorin:synergism of action between decorin and carboplatin. Cancer Res, 1999,59:6192-6196.
65. Koninger J, Giese NA, di Mola FF, et al. Overexpressed decorin in pancreatic cancer: potential tumor growth inhibition and attenuation of chemotherapeutic action. Clin Cancer Res,2004,10:4776-4783.
66. Tralhao JG, Schaefer L, Micegova M,et al. In viva selective and distant killing of cancer ceUs using adenovirus-mediated decorin gene transfer. FASEB J,2003, 17:464-466.
67. Goldoni S, Seidler DG, Heath J, et al.An anti-metastatic role for decorin in breast cancer. Am J Pathol,2008,173:844-855.
68. Shintani K, Matsumine A, Kusuzaki K,et al.Decorin suppresses lung metastases of murine osteosarcoma. Oncol Rep,2008,19:1533-1539.
69. Kentaro Araki, Hiroki Wakabayashi, Ken Shintani,et al.Decorin Suppresses Bone Metastasis in a Breast Cancer Cell Line.Oncology,2009,77:92-99.
2. Lieberman DA,Weiss DG, Harford WV, et al. Five-year colon surveillance after screening colonoscopy. Gastroenterology,2007,133:1077-1085.
3. Imperiale TF,Sox HC.Guidelines for surveillance intervals after polypectomy: coping with the evidence.Ann Intern Med,2008,148:477-479.
4. Gupta S.Colorectal Polyps:The Scope and Management of the Problem.Am J Med Sci,2008,336:407-417.
5. Sheikh RA,Min BH, Yasmeen S,et al.Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas.Dig Dis Sci,2003,48:223-229.
6. Goldoni S,Iozzo RV.Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs.Int J Cancer,2008,123:2473-2479.
7. Seidler DG, Schaefer L, Robenek H, et al. A physiologic three-dimensional cell culture svstem to investigate the role of decorin in matrix organization and cell survival. Biochem Biophys Res Commun,2005,332:1162-1170.
8. Daniela G. Seidler,Silvia Goldoni,Christopher Agnew,et al. Decorin protein core inhibits in vivo cancer growth and metabolism by hindering epidermal growth factor receptor function and triggering apoptosis via caspase-3 activation. J Biol Chem,2006,281:26408-26418.
9. Moscatello DK, Santra M, Mann DM, et al:Decorin suppresses tumor cell growth by activating the epidermal growth factor receptor. J Clin Ivest,1998,101:406-412.
10. Stander M,Naumann U,Dumitrescu L, et al.Decorin gene transfer-mediated suppression of TGF beta synthesis abrogates experimental malignant glioma growth in vivo.Gene Ther,1998,5:1187-1194.
11. Sandra Troup,Catherine Njue, Erich V. Kliewer, et al.Reduced Expression of the Small Leucine-rich Proteoglycans,Lumican, and Decorin Is Associated with Poor Outcome in Node-negative Invasive Breast Cancer. Clin Cancer Res,2003, 9:206-214.
12. Salomaki HH,Sainio AO,Soderstrom M,et al. Differential expression of decorin by human malignant and benign vascular tumors. J Histochem Cytochem,2008, 56:639-646.
13. Arnaldi LA, Borra RC, Maciel RM,et al.Gene expression profiles reveal that DCN, DIO1, and DIO2 are underexpressed in benign and malignant thyroid tumors.Thyroid,2005,15:210-221.
14. Akihiko Matsumine,Ken Shintani,Katsuyuki Kusuzaki,et al.Expression of Decorin, a Small Leucine-Rich Proteoglycan, as a Prognostic Factor in Soft Tissue Tumors.J Surg Oncol,2007,96:411-418.
15. Santra M, Skorski T, Calabretta B,et al.De novo decorin gene expression suppresses the malignant phenotype in human colon cancer cells.Proc Natl Acad Sci U S A. 1995,92:7016-7020.
16. Augoff K,Rabczynski J,Tabola R,et al.Immunohistochemical study of decorin expression in polyps and carcinomas of the colon.Med Sci Monit,2008,14:530-535.
17. Bi X,Tong C, Dockendorff A,et al. Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation.Carcinogenesis, 2008,29:1435-1440.
18.全国大肠癌病理研究组.全国大肠癌病理研究统一规范.全国大肠癌病理读片会,杭州,1982,12-16.
19. V T Labropoulou,A D Theocharis,1 P Ravazoula,et al.Versican but not decorin accumulation is related to metastatic potential and neovascularization in testicular germ cell tumours.Histopathology,2006,49:582-593.
20. Giacosa A,Frascio F,Munizzi F.Epidemiology of colorectalpolyps.Tech Coloproctol, 2004,8(Suppl2),a243.
21.李伏娥,叶红军,李坚等.796例大肠息肉的临床、内镜及病理观察.中南大学学报(医学版),2005,30：463.
22. Bond JH.Colon polyps and cancer.Endoscopy,2005,37:208.
23.郏芝田.胃肠病学.第3版.北京：人民卫生出版社,2000：846.
24. Sanderson SJ, Ewing Sk, Wiehr CL, et al. Aberrant expression of MUC5AC and MUC6 gastric mucin genes in colorectal polyps.InI J Cancer,1999,80:210-218.
25.黄超,黄梅芳,朱尤庆.大肠息肉946例临床分析.实用医学杂志,2005,18：2048-2049.
26.王永华,卢忠生,王向东.不同病理类型结直肠息肉的差别.胃肠病学和肝病学杂志,2003,12：563-565.
27. Lieberman DA,W eiss DG. Five year surveillance of patients with adenomas or colorectal cancer at screening colonoscopy (results from the VA Cooperative Study#380).Gastroenterology,2004,126:A22.
28.Noshirwani KC,van Stolk RU,Rybicki LA,et al. Adenoma size and number are predictive of adenoma recurrence(implications for surveillance colonoscopy). Gastrointest Endosc,2000,51:433-437.
29.陈灏珠.实用内科学.第12版.北京：人民卫生出版社,2005：1934.
30. Lieberman DA.Targted colon cancer screening a concept whose time has almost come.Am J Gastroenterol,1992,87:1085-1093.
31.梅俏,鲍峻峻,许建明,等.228例大肠高危腺瘤性息肉的回顾性分析[J].安徽医学,2008,29：392-394.
32. Yang G,Zheng W,Sun QR,et al.Pathologic features of initial adenomas as predictors for metachronous adenomas of the rectum.J Natl Cancer Inst,1998,90:1661-1665.
33. Bertario L, Russo A, Sala P,et al. Predictors of metachronous colorectal neoplasms in sporadic adenoma patients. Int J Cancer 2003,105:82-87.
34.欧希龙,孙为豪,曹大中,等.大肠息肉及恶性肿瘤活检与整体病理诊断差异性分析.中华消化内镜杂志,2004,21：277-279.
35. Sung SY,Hsieh CL, Wu D,et al.Tumor microenvironment promotes cancer progression,metastasis,and therapeutic resistance.Curr Probl Cancer.2007,31: 36-100.
36. Schaefer L, Iozzo RV.Biological functions of the small leucine-rich proteoglycans: from genetics to signal transduction.J Biol Chem.2008,283:21305-21309.
37. Wegrowski Y,Maquart FX.Involvement of stromal proteoglycans in tumour progression.Crit Rev Oncol Hematol.2004,49:259-268.
38. Iozzo RV.The family of the small leucine-rich proteoglycans:key regulators of matrix assembly and cellular growth.Crit Rev Biochem Mol Biol.1997,32:141-174.
39. De Luca A,Santra M, Baldi A,et al. Decorin-induced growth suppression is associated with up-regulation of p21, an inhibitor of cyclin-dependent kinases. J Biol Chem.1996,271:18961-18965.
40. Iozzo RV,Moscatello DK, McQuillan DJ,et al.Decorin is a biological ligand for the epidermal growth factor receptor. J Biol Chem 1999,274:4489-4492.
41. Moscatello DK, Santra M,Mann DM,et al.Decorin suppresses tumor cell growth by activating the epidermal growth factor receptor. J Clin Invest.1998,101:406-412.
42. Derynck R,Akhurst RJ,Balmain A.TGF-beta signaling in tumor suppression and cancer progression. Nat Genet.2001,29:117-129.
43. Davies Cde L,Melder RJ,Munn LL, et al.Decorin inhibits endothelial migration and tube-like structure formation: Role of thrombospondin-1. Microvasc Res. 2001,62:26-42.
44. Silvia Goldoni,Ashley Humphries,Alexander Nystrom,et al.Decorin is a novel antagonistic ligand of the Met receptor.J Cell Biol,2009,185:743-754.
45. Grant DS,Yenisey C, Rose RW, et al.Decorin suppresses tumor cell-mediated angiogenesis. Oncogene,2002,21:4765-4777.
46. Petit AMV, Rak J,Hung M-C,et al. Neutralizing antibodies against epidermal growth factor and Erb-2/neu receptor tyrosine kinases down-regulated vascular endothelial growth factor production by tumor cells in vitro and in vivo.Angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol. 1997,151:1523-1530.
47.赵素莲,王桂琴,田树华,等.Decorin对肝癌细胞株凋亡作用的研究.肿瘤防治杂志,2002,9：235-237.
48. Biglari A,Bataille D,Naumann U, et al.Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model. Cancer Gene Ther. 2004,11:721-732.
49. Nash MA,Deavers MT, Freedman RS.The expression of decorin in human ovarian tumors.Clin Cancer Res.2002,8:1754-1760.
50. Tralhao JG,Schaefer L,Micegova M,et al.In viva selective and distant killing of cancer cells using adenovirus-mediated decorin gene transfer.FASEB J,2003,17:464-466.
51.Kentaro Araki,Hiroki Wakabayashi,Ken Shintani,et al.Decorin Suppresses Bone Metastasis in a Breast Cancer Cell Line.Oncology,2009,77:92-99.
52. Koninger J,Giese NA, di Mola FF, et al. Overexpressed decorin in pancreatic cancer: potential tumor growth inhibition and attenuation of chemotherapeutic action. Clin Cancer Res,2004,10:4776-4783.
53.戎彪学,蔡曦光,马慧,等Decorin mRNA和p57 mRNA在非小细胞肺癌中的表达及其临床意义.临床肿瘤学杂志,2006,11：331-335.
54.傅锦业,吴毅,王卓颖,等Decorin在甲状腺恶性肿瘤中的表达及其临床意义. 中华内分泌代谢杂志.2008,24：68-69.
55. Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med.1992,326:658-662.
56.朱雄增.学习和掌握肿瘤的WHO分类,提高病理诊断和研究的水平.中华病理学杂志,2006,35：649.
57. Laiyemo AO,Murphy G, Albert PS, et al.Postpolypectomy colonoscopy surve-illance guidelines:predictive accuracy for advanced adenoma at 4 years.Ann Intern Med.2008,148:419-426.
1. Sung SY,Hsieh CL, Wu D,et al.Tumor microenvironment promotes cancer progression,metastasis,and therapeutic resistance.Curr Probl Cancer.2007, 31:36-100.
2. lozzo RV.The family of the small leucine-rich proteoglycans:key regulators of matrix assembly and cellular growth.Crit Rev Biochem Mol Biol.1997,32:141-174.
3. Wegrowski Y,Maquart FX.Involvement of stromal proteoglycans in tumour progression.Crit Rev Oncol Hematol.2004,49:259-268.
4. Schaefer L, lozzo RV. Biological functions of the small leucine-rich proteoglycans: from genetics to signal transduction. J Biol Chem.2008,283:21305-21309.
5. lozzo RV.The biology of the small leuclne-rich proteoglycans functional network of interactive proteins. J Biol Chem,1999,274:18843-18846.
6. Goldoni S,Iozzo RV.Tumor microenvironment:Modulation by decorin and related molecules harboring leucine-rich tandem motifs.Int J Cancer,2008,123:2473-2479.
7. Kresse H,Schonherr E.Proteoglycans the extracellular matrix and growth control.J Cell Physiol,2001,189:266-274.
8. Bi Y, Stueltens CH, Kilts T, et al.Extracellular matrix proteoglycans control the fate of bone marrow stromal cells. J Biol Chem.2005,280:30481-30489.
9. Jarvelainen H, Puolakkainen P, Pakkanen S, et al.. A role for decorin in cutaneous wound healing and angiogenesis. Wound Repair Regen 2006; 14:443-452.
10. Seidler DG, Schaefer L, Robenek H, et al. A physiologic three-dimensional cell culture svstem to investigate the role of decorin in matrix organization and cell survival. Biochem Biophys Res Commun,2005,332:1162-1170.
11. Akihiko Matsumine,Ken Shintani,Katsuyuki Kusuzaki,et al.Expression of Decorin, a Small Leucine-Rich Proteoglycan, as a Prognostic Factor in Soft Tissue Tumors.J Surg Oncol,2007,96:411-418.
12. Sandra Troup, Catherine Njue, Erich V. Kliewer, et al. Reduced Expression of the Small Leucine-rich Proteoglycans,Lumican, and Decorin Is Associated with Poor Outcome in Node-negative Invasive Breast Cancer. Clin Cancer Res,2003, 9:206-214.
13..Iozzo RV,Moscatello DK, McQuillan DJ,et al.Decorin is a biological ligand for the epidermal growth factor receptor. J Biol Chem 1999,274:4489-4492.
14. Moscatello DK, Santra M,Mann DM,et al.Decorin suppresses tumor cell growth by activating the epidermal growth factor receptor. J Clin Invest.1998,101:406-412.
15. Csordas G, Santra M, Reed CC, et al.Sustained down-regulation of the epidermal growth factor receptor by decorin. A mechanism for controlling tumor growth in vivo. J Biol Chem,2000,275:32879-32887.
16. De Luca A,Santra M, Baldi A,et al. Decorin-induced growth suppression is associated with up-regulation of p21, an inhibitor of cyclin-dependent kinases. J Biol Chem.1996,271:18961-18965.
17. Schonherr E, Levkau B, Schaefer L,et al.Decorin-mediated signal transduction in endothelial cells. Involvement of Akt/protein kinase B in up-regulation of p21(WAF1/CIP1) but not p27(KIP1).J Biol Chem.2001,276:40687-40692.
18. Reed CC,Gauldie J,Iozzo RV.Suppression of tumorigenicity by Adenovirus-mediated gene transfer of decorin.Oncogene,2002,21:3688-3695.
19. Csordas G,Santra M,Reed CC,et al.Sustained down-regulation of the epidermal growth factor receptor by decorin:A mechanism for controlling tumor growth in vivo.J Biol Chem,2000,275:32879-32887.
20. Daniela G. Seidler, Silvia Goldoni, Christopher Agnew,et al. Decorin protein core inhibits in vivo cancer growth and metabolism by hindering epidermal growth factor receptor function and triggering apoptosis via caspase-3 activation. J Biol Chem,2006,281:26408-26418.
21.Schonherr E, Sunderkotter C, Iozzo RV, et al. Decorin, a novel player in the insulin-like growth factor system. J Biol Chem,2005,280:15767-15772.
22. Schaefer L, Tsalastra W, Babelova A, et al. Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-1 receptor and mammalian target of rapamycin. Am J Pathol,2007,170:301-315.
23. Schonherr E, Bodo Levkau, Schaefer L,et al.Decorin-mediated Signal Transduction in Endothelial Cells.J Biol Chem,2001,276:40687-40692.
24. Stella MC, Trusolino L,Pennacehietti S, et al. Negative feedback regulation of met-dependent invasive growt h by notch. Mol Cell Biol,2005,25:3982-3996.
25. Silvia Goldoni, Ashley Humphries, Alexander Nystrom,et al.Decorin is a novel antagonistic ligand of the Met receptor.J Cell Biol,2009,185:743-754.
26. Enrique Brandanl, Claudio Retamal, Claudio Cabello-Verrugio,et al.The Low Density Lipoprotein Receptor-related Protein Functions as an Endocytic Receptor for Decorin. J Biol Chem,2006,281:31562-31571.
27. Claudio Cabello-Verrugiol.Enrique Brandan.A novel modulatory mechanism of transforming growth factor-b signaling through decorin and LRP-1.J Biol Chem, 2007,282:18842-18845.
28. Derynck R,Akhurst RJ,Balmain A.TGF-beta signaling in tumor suppression and cancer progression. Nat Genet.2001,29:117-129.
29. Marko S,Ulrike N,Wolfgang W,et al.Transforming growth factorβand p-21:multiple molecular targets of decorin-mediated suppression of euplastic growdth.J Cell rrisstte Res.1999,296:221.
30. Davies Cde L,Melder RJ,Munn LL, et al.Decorin inhibits endothelial migration and tube-like structure formation:Role of thrombospondin-1. Micro vasc Res.2001, 62:26-42.
31.tander M,Naumann U,Dumitrescu L, et al.Decorin gene transfer-mediated suppression of TGF beta synthesis abrogates experimental malignant glioma growth in vivo.Gene Ther,1998,5:1187-1194.
32. Xiuli Bi, Tong C, Dokendorff A, et al. Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis,2008,29:1435-1440.
33. Grant DS, Yenisey C, Rose RW, et al.Decorin suppresses tumor cell-mediated angiogenesis. Oncogene,2002,21:4765-4777.
34. Petit AMV, Rak J, Hung M-C, et al.Neutralizing antibodies against epidermal growth factor and Erb-2/neu receptor tyrosine kinases down-regulated vascular endothelial growth factor production by tumor cells in vitro and in vivo. Angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 1997;151:1523-1530.
35. Salomaki HH, Sainio AO, Soderstrom M, et al. Differential expression of decorin by human malignant and benign vascular tumors. J Histochem Cytochem, 2008,56:639-646.
36.赵素莲,王桂琴,田树华,等.Decorin对肝癌细胞株凋亡作用的研究.肿瘤防治杂志,2002,3：235-237.
37. Jorg Koninger,Nathalia A. Giese,Fabio Francesco di Mola, et al.Overexpressed Decorin in Pancreatic Cancer:Potential Tumor Growth Inhibition and Attenuation of Chemotherapeutic Action.Clin Cancer Res.2004,10:4776-4783.
38. Theocharis AD, Vynios DH, Papageorgakopoulou N, et al.Altered content composition and structure of glycosaminoglycans and proteoglycans in gastric carcinoma. Int J Biochem Cell Biol.2003;35:376-390.
39. Miyasaka Y, Enomoto N, Nagayama K, et al.Analysis of differentially expressed genes in human hepatocellular carcinoma using suppression subtractive hybridization. Br J Cancer.2001;85:228-234.
40. McDoniels-Silvers AL, Nimri CF, Stoner GD, et al. Differential gene expression in human lung adenocarcinomas and squamous cell carcinomas. Clin Cancer Res 2002;8:1127-1138.
41.Leygue E, Snell L, Dotzlaw H, et al.Lumican and decorin are differentially expressed in human breast carcinoma. J Pathol.2000;192:313-320.
42. Reed CC, Waterhouse A, Kirby S, et al.Decorin prevents metastatic spreading of breast cancer. Oncogene 2005;24:1104-1110.
43. Michael A. Nash, Michael T. Deavers, Ralph S. Freedmanl.The Expression of Decorin in Human Ovarian Tumors.Clin Cancer Res.2002,8:1754-1760.
44. Grisaru D, Hauspy J, Prasad M, et al.Microarray expression identification of differentially expressed genes in serous epithelial ovarian cancer compared with bulk normal ovarian tissue and ovarian surface scrapings.Oncol Rep, 2007,18:1347-1356.
45. Arnaldi LA, Borra RC, Maciel RM,et al.Gene Expression Profiles Reveal that DCN, DIO1,and DIO2 Are Underexpressed in Benign and Malignant Thyroid Tumors.Thyroid.2005,15:210-221.
46.傅锦业, 吴毅, 王卓颖.伴颈部淋巴结转移的甲状腺乳头状癌的基因差异表达.中国癌症杂志,2006,16：980-984.
47. Adany R, Heimer R, Caterson B, et al. Altered expression of chondroitin sulfate proteoglycan in the stroma of human colon carcinoma.Hypomethlation of PG-40 gene correlates with increased PG-40 content and mRNA levels. J Biol Chem, 1990,265:11389-11396.
48. Augoff K, Rabczynski J, Tabola R,et al.Immunohistochemical study of decorin expression in polyps and carcinomas of the colon.Med Sci Monit,2008,14:530-535.
49. Santra M, Skorski T, Calabretta B,et al. De novo decorin gene expression suppresses the malignant phenotype in human colon cancer cells. Proc Natl Acad Sci USA 1995,92:7016-7020.
50. Biglari A, Bataille D, Naumann U, et al. Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model. Cancer Gene Ther, 2004,11:721-732.
51. Pan S, Cheng L, White JT, et al.Quantitative proteomics analysis integrated with microarray data reveals that extracellular matrix proteins, catenins, and p53 binding protein 1 are important for chemotherapy response in ovarian cancers.OMICS. 2009,13:345-354.
52. Goldoni S,Iozzo RV.Tumor microenvironment:Modulation by decorin and related molecules harboring leucine-rich tandem motifs.Int J Cancer,2008,123:2473-2479.
53.操海萍,舒振波,王维忠,等.核心蛋白聚糖在乳腺癌中表达的探讨.中国肿瘤临床,2006,33：1105-1108.
54.戎彪学,蔡曦光,马慧,等Decorin mRNA和p57 mRNA在非小细胞肺癌中的表达及其临床意义.临床肿瘤学杂志,2006,11：331-335.
55.傅锦业,吴毅,王卓颖,等Decorin在甲状腺恶性肿瘤中的表达及其临床意义.中华内分泌代谢杂志,2008,24：68-69.
56. Crnogorae-Jurcevic T,Efthimiou E,Capelli P,et al.Gene expression profiles of pancreatic cancer and stromal desmoplasia.Oneogene,2001,20:7437-7446.
57. Skandalis SS, Theocharis AD, Theocharis DA, et. Al.Matrix proteoglycans are markedly affected in advanced laryngeal squamous cell carcinoma. Biochem Biophys Acta 2004;1689:152-161.
58. Brown LF, Guidi AJ, Schnitt SJ, et al. Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast. Clin Cancer Res 1999;5:1041-1056.
59. Koninger J, Giese T, di Mola FF,et,al. Pancreatic tumor cells influence the composition of the extracellular matrix. Biochem Biophys Res Commun, 2004,322:943-949.
60. Merle B, Durussel L, Delmas PD, et al. Decorin inhibits cell migration through a process requiring its glycosaminoglycan side chain. J Cell Biochem, 1999,75：538-546.
61.张玉成,王雅丽,杜珍武,等.核心蛋白聚糖在HepG_2细胞中的表达与作用.山东医药,2008,7：35-37.
62.赵斌燕,齐峰Decorin因子对人胃癌细胞及其表达的MG7蛋白的作用.中华医学研究杂志,2006,1：19-20.
63. Santra M, Skorski T, Calabretta B, et al. De novo deeorin gene expression suppresses the malignant phenotype in human colon cancer cells. Proc Natl Acad Sci U S A,1995,92:7016-7020.
64. Nash MA, Loercher AE, Freedman RS. In vitro growth inhibition of ovarian cancer cells by decorin:synergism of action between decorin and carboplatin. Cancer Res, 1999,59:6192-6196.
65. Koninger J, Giese NA, di Mola FF, et al. Overexpressed decorin in pancreatic cancer: potential tumor growth inhibition and attenuation of chemotherapeutic action. Clin Cancer Res,2004,10:4776-4783.
66. Tralhao JG, Schaefer L, Micegova M,et al. In viva selective and distant killing of cancer ceUs using adenovirus-mediated decorin gene transfer. FASEB J,2003, 17:464-466.
67. Goldoni S, Seidler DG, Heath J, et al.An anti-metastatic role for decorin in breast cancer. Am J Pathol,2008,173:844-855.
68. Shintani K, Matsumine A, Kusuzaki K,et al.Decorin suppresses lung metastases of murine osteosarcoma. Oncol Rep,2008,19:1533-1539.
69. Kentaro Araki, Hiroki Wakabayashi, Ken Shintani,et al.Decorin Suppresses Bone Metastasis in a Breast Cancer Cell Line.Oncology,2009,77:92-99.