骨桥蛋白与基质金属蛋白酶-9在胰腺癌中的表达及其临床意义
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摘要
目的(1)检测骨桥蛋白(osteopontin,OPN)与基质金属蛋白酶-9(matrix metallo- -proteinase-9,MMP-9)在胰腺癌组织中的表达,分析其与临床病理特征的关系。(2)探讨胰腺癌中OPN与MMP-9的相互关系及可能的作用机制。(3)评估血清OPN检测在胰腺癌早期诊断及预后判断中的价值。
方法(1)免疫组织化学UltraSensitiveT SP法检测OPN与MMP-9在50例胰腺癌、30例癌旁组织中的表达。(2)ELISA法和电化学发光免疫分析法检测30例胰腺癌患者及20例健康志愿者的血清OPN、CA199、CEA水平。(3)ROC曲线法比较OPN、CA199、CEA诊断胰腺癌的敏感度和特异度,评估OPN在胰腺癌诊断中的价值。
结果(1)OPN和MMP-9在胰腺癌组织中的阳性表达率(64.0%,62.0%)明显高于其在癌旁组织中的阳性表达率(20.0%,26.6%) (P<0.01)。(2)OPN和MMP-9的表达均与肿瘤的分化程度,TNM分期及淋巴结转移有关(P<0.05)。(3)胰腺癌组织中OPN与MMP-9的表达呈正相关(r=0.53,P<0.01)。(4)胰腺癌患者血清OPN、CA199、CEA的水平(79.2±42.1ng/ml,397.5±360.0U/ml,4.3±3.8ug/ml)高于健康志愿者的血清OPN、CA199、CEA的水平(31.2±25.6 ng/ml,37.0±26.2U/ml,2.3±2.7ug/ml)(P<0.01或0.05)。(5)联合检测血清OPN、CA199、CEA的诊断胰腺癌的敏感度(96.7%)高于单独检测任一指标的敏感度(56.7%,86.6%,36.4%)(P<0.05)。
结论(1)OPN与MMP-9在胰腺癌组织中均呈高表达,其表达与肿瘤的侵袭转移密切相关。(2)胰腺癌组织中OPN与MMP-9的表达呈正相关,两者在胰腺癌发生发展中可能起协同作用。(3)胰腺癌患者血清OPN水平与肿瘤分期及远处转移有关,可作为临床评估病情,监测疗效、判断预后的重要指标。(4)联合检测血清OPN、CA199与CEA水平有助于提高胰腺癌的诊断率,对于胰腺癌筛查有重要意义。
Objective ( 1 ) To detect the expression of osteopontin (OPN) and matrix metalloproteinase-9(MMP-9) in pancreatic cancer tissue, and analyse its relationship with clinicopathological characteristics.(2) To explore the correlation between OPN and MMP-9 of pancreatic cancer and their possible mechanism of operation.(3) To evaluate the value of OPN in the early diagnosis and the prognosis assessment of pancreatic cancer.
Methods(1)Immunohistochemical UltraSensitiveT SP method was used to detect the expression of OPN and MMP-9 in 50 cases of pancreatic cancer tissues and 30 cases of tumor-adjacent tissues.(2)The Serum levels of OPN,CEA,CA199 in 30 patients with pancreatic cancer and 20 healthy volunteers were measured by enzyme-linked immunosorbent assay and electrical chemiluminescence immunoassay.(3)Receiver operating characteristics curve (ROC) was used to compare the diagnostic sensitivity and specificity of OPN, CEA, and CA199 in the patients with pancreatic cancer , The value of OPN in the diagnosis of pancreatic cancer was assessed.
Results (1)The positive rates of OPN and MMP-9 (64.0%,62.0%)in Pancreatic cancer tissue was significantly higher than in tumor-adjacent tissues(20.0%,26.6%) (P<0.05)(.2)The expression of OPN and MMP-9 were correlated with tumor differentiation,TNM stage and lymph node metastases of pancreatic cancer (P< 0.05).(3)There was a positive correlation between the expression of OPN and MMP-9 in pancreatic cancer tissue (r=0.53,P<0.01). (4)The serum levels of OPN, CA199 and CEA in patients with pancreatic cancer(79.2±42.1 ng/ml,397.5±360.0U/ml,4.3±3.8ug/ml)were higher than in healthy subjects(31.2±25.6 ng/ml,37.0±26.2U/ml,2.3±2.7ug/ml)(P<0.01or 0.05).(5)The sensitivity of combined detection with serum OPN, CEA, or CA199(96.7%) was higher than respective detection of OPN, CEA, or CA199(56.7%,86.6%,36.4%) in diagnosis of pancreatic cancer.
Conclusion(1)OPN and MMP-9 are highly expressed in Pancreatic cancer tissues. The expression of them is closely related to the invasion and metastases of pancreatic cancer.(2)The expression of OPN and MMP-9 is positive correlated and probably coordinated in the occurrence and development of pancreatic cancer(.3)The serum osteopontin is closely related to distant metastasis and TNM stages of the Pancreatic cancer.The serum OPN may be an important maker to assess the outcome of pancreatic cancer and to monitor the efficacy of clinical treatment, to determine prognosis.(4)Combined detection with serum OPN, CA199, CEA can improve the rate of diagnosis. It also has important significance for the screening of pancreatic cancer.
方法(1)免疫组织化学UltraSensitiveT SP法检测OPN与MMP-9在50例胰腺癌、30例癌旁组织中的表达。(2)ELISA法和电化学发光免疫分析法检测30例胰腺癌患者及20例健康志愿者的血清OPN、CA199、CEA水平。(3)ROC曲线法比较OPN、CA199、CEA诊断胰腺癌的敏感度和特异度,评估OPN在胰腺癌诊断中的价值。
结果(1)OPN和MMP-9在胰腺癌组织中的阳性表达率(64.0%,62.0%)明显高于其在癌旁组织中的阳性表达率(20.0%,26.6%) (P<0.01)。(2)OPN和MMP-9的表达均与肿瘤的分化程度,TNM分期及淋巴结转移有关(P<0.05)。(3)胰腺癌组织中OPN与MMP-9的表达呈正相关(r=0.53,P<0.01)。(4)胰腺癌患者血清OPN、CA199、CEA的水平(79.2±42.1ng/ml,397.5±360.0U/ml,4.3±3.8ug/ml)高于健康志愿者的血清OPN、CA199、CEA的水平(31.2±25.6 ng/ml,37.0±26.2U/ml,2.3±2.7ug/ml)(P<0.01或0.05)。(5)联合检测血清OPN、CA199、CEA的诊断胰腺癌的敏感度(96.7%)高于单独检测任一指标的敏感度(56.7%,86.6%,36.4%)(P<0.05)。
结论(1)OPN与MMP-9在胰腺癌组织中均呈高表达,其表达与肿瘤的侵袭转移密切相关。(2)胰腺癌组织中OPN与MMP-9的表达呈正相关,两者在胰腺癌发生发展中可能起协同作用。(3)胰腺癌患者血清OPN水平与肿瘤分期及远处转移有关,可作为临床评估病情,监测疗效、判断预后的重要指标。(4)联合检测血清OPN、CA199与CEA水平有助于提高胰腺癌的诊断率,对于胰腺癌筛查有重要意义。
Objective ( 1 ) To detect the expression of osteopontin (OPN) and matrix metalloproteinase-9(MMP-9) in pancreatic cancer tissue, and analyse its relationship with clinicopathological characteristics.(2) To explore the correlation between OPN and MMP-9 of pancreatic cancer and their possible mechanism of operation.(3) To evaluate the value of OPN in the early diagnosis and the prognosis assessment of pancreatic cancer.
Methods(1)Immunohistochemical UltraSensitiveT SP method was used to detect the expression of OPN and MMP-9 in 50 cases of pancreatic cancer tissues and 30 cases of tumor-adjacent tissues.(2)The Serum levels of OPN,CEA,CA199 in 30 patients with pancreatic cancer and 20 healthy volunteers were measured by enzyme-linked immunosorbent assay and electrical chemiluminescence immunoassay.(3)Receiver operating characteristics curve (ROC) was used to compare the diagnostic sensitivity and specificity of OPN, CEA, and CA199 in the patients with pancreatic cancer , The value of OPN in the diagnosis of pancreatic cancer was assessed.
Results (1)The positive rates of OPN and MMP-9 (64.0%,62.0%)in Pancreatic cancer tissue was significantly higher than in tumor-adjacent tissues(20.0%,26.6%) (P<0.05)(.2)The expression of OPN and MMP-9 were correlated with tumor differentiation,TNM stage and lymph node metastases of pancreatic cancer (P< 0.05).(3)There was a positive correlation between the expression of OPN and MMP-9 in pancreatic cancer tissue (r=0.53,P<0.01). (4)The serum levels of OPN, CA199 and CEA in patients with pancreatic cancer(79.2±42.1 ng/ml,397.5±360.0U/ml,4.3±3.8ug/ml)were higher than in healthy subjects(31.2±25.6 ng/ml,37.0±26.2U/ml,2.3±2.7ug/ml)(P<0.01or 0.05).(5)The sensitivity of combined detection with serum OPN, CEA, or CA199(96.7%) was higher than respective detection of OPN, CEA, or CA199(56.7%,86.6%,36.4%) in diagnosis of pancreatic cancer.
Conclusion(1)OPN and MMP-9 are highly expressed in Pancreatic cancer tissues. The expression of them is closely related to the invasion and metastases of pancreatic cancer.(2)The expression of OPN and MMP-9 is positive correlated and probably coordinated in the occurrence and development of pancreatic cancer(.3)The serum osteopontin is closely related to distant metastasis and TNM stages of the Pancreatic cancer.The serum OPN may be an important maker to assess the outcome of pancreatic cancer and to monitor the efficacy of clinical treatment, to determine prognosis.(4)Combined detection with serum OPN, CA199, CEA can improve the rate of diagnosis. It also has important significance for the screening of pancreatic cancer.
引文
[1] Nitecki SS,Sarr MG,Colby TY,et al. Long-term survival after resection for ductal adeno- -carcinoma of the pancreas. Is it really improving?Ann Sur,1995,221(1):59-63.
[2]詹海勇,黄聪武,林銮群,等.血清糖链抗原19-9和糖链抗原242诊断胰腺癌的临床价值.疑难病杂志. 2006, 5(3):186.
[3] Wai PY, Kuo PC. The role of osteopontin in tumor metastasis. J Surg Res, 2004, 121(2): 228-241.
[4] Kolb A, Kleeff J, Guweidhi A, et al. Osteopontin influences the invasiveness of pancreatic cancer cells and is increased in neoplastic and inflammatory conditions. Cancer Biol Ther. 2005 Jul;4(7):740-746.
[5] Coppola D,Szabo M,Boulware D,et al.Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin Cancer Res. 2004;10(1 Pt 1):184-190.
[6] Nagase H. Activation mechanisms of matrix metalloproteinases. Biol Chem, 1997, 378:151-160.
[7] Shue JR, Fong TH, Liu CM, et al. Expression of matrix metalloproteinase-9 in human platelets regulation of platelet activation in vitro and in vivo studies[J]. Br J Pharmacol, 2004,143(1):193-201.
[8] Rooprai HK,vanMeter TE,Robinson SD,et a1.Expression of MMP2 and 9 in short-term Cultures of meningioma:influence of histological subtype[J].Int J Mol Med,2003,12(6): 977-981.
[9] Rangaswami H, Kundu GC. Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways. Oncol Rep. 2007,18(4): 909-915.
[10]张东涛,袁静,杨力,等.骨桥蛋白在胃癌中的表达及胃癌侵袭转移的关系[J].中华肿瘤杂志,2005,27(3):167-169.
[11] Angelucci A,Festuccia C,Gravina GL,et al. osteopontin enhances the cell proliferation induced by the epidermal growth factor in human prostate cancer cells [J] Prostate,2004, 59(2):157.
[12] Kunigal S, Lakka SS, Joseph P, et al. Matrix metalloproteinase-9 inhibition down- regulates radiation-induced nuclear factor-kappa B activity leading to apoptosis in breast tumors. Clin Cancer Res. 2008 Jun 1;14(11):3617-3626.
[13] Lowenfels AB,Maisonneuve P.Epidemiology and prevention of pancreatic cancer,Jpn J Clin Oncol,2004,34:238-244.
[14] Urquidi V , Sloan D, Kawai K,et al. Contrasting expression of thrombospondin-1 and osteopontin correlates with absence or presence of metastatic phenotype in an isogenic model of spontaneous human breast cancer metastasis[J]. Clin Cancer Res, 2002,8:61-74.
[15] Senger DR, Wirth DF, Hynes RO.Transformed mammalian cells secrete specific proteins and phosphoproteins[J].Cell.1979,16(4): 885-893.
[16] Pryczynicz A, Guzińska-Ustymowicz K, Dymicka-Piekarska V, et al. Expression of matrix metalloproteinase 9 in pancreatic ductal carcinoma is associated with tumor metastasis formation[J]. Folia Histochem Cytobiol. 2007;45(1):37-40.
[17]王维新,张国新,都波,等,骨桥蛋白、CD44v6在胰腺癌中的表达及其与临床病理特征的关系[J]南京医科大学学报(自然科学版)2007,27(8):801-803.
[18] Sedivy R,Peters K,Kloppel G. Osteopontin expression in ductal adenocarcinomas and undifferentiated carcinomas of the pancreas.Virchows Arch. 2005;446(1):41-45.
[19] Weber GF, Zawaideh S,Hikita S, et a.l Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophagemigration and activation[J]. J Leukoc Biol, 2002, 72(4):752-761.
[20] Denhardt DT,Mistretta D,Chambers AF,et al.Transcriptional regulation of osteopontin and the metastatic phenotype:evidence for a Rasactivated enhancer in the human OPNpromoter〔J〕.Clin Exp Metastasis,2003,20(1):77.
[21] Giannopoulos G, Pavlakis K, Parasi A, et al. The expression of matrix metalloproteinases -2 and -9 and their tissue inhibitor 2 in pancreatic ductal and ampullary carcinoma and their relation to angiogenesis and clinicopathological parameters[J]. Anticancer Res. 2008,28(3B):1875-81.
[22] Furger KA,Allan AL,et al. Beta3 integrin expression increases breast carcinoma cell responsiveness to the malignaney-enhancing effeets of osteopontin[J].Mol Cancer Res. 2003,l(11):810-819.
[23] Jones JL,Walker RA. Control of martix metalloproteinase activity in cancer[J].J Pathol, 1997,183(4):377-379.
[24] Agrez M ,Gu X, Turton J,et al.The alpha v beta 6 integrin induces gelatinase B secretion in colon cancer cells. Int J Cancer 1999; 81(1): 90-97.
[25] Liu SJ, Hu GF, Liu YJ, et al. Effect of human osteopontin on proliferation, trans- -migration and expression of MMP-2 and MMP-9 in osteosarcoma cells. Chin Med J (Engl), 2004, 117(2): 235-240.
[26] Jubo NS,Uede T,Kon S,et al. Vascular endothelial growth factor and osteopontin in stageⅠlung adenocarcinoma[J].Am J Respir Crit Care Med,1999,160(4):1269-1273.
[27] Rangaswami H, Bulbule A, Kundu GC. Nuclear factor inducing kinase plays a crucial role in osteopontin-induced MAPK/IKappaBalpha kinase-dependent nuclear factor kappaB-mediated promatrix metalloproteinase-9 activation [J]. J Biol Chem, 2004, 279 (37):38921-38935.
[28]宋杏丽,李秉慧,韩梅等.骨桥蛋白诱导的黏着斑激酶信号途径参与大肠癌的侵袭与转移[J].中国老年学杂志,2005;25(9):1081-1083.
[29]杨力,张东涛,郭新宁.骨桥蛋白和核因子-KB在侵袭转移性胃癌中的表达[J].中国肿瘤临床,2004,31(16):901-903.
[30] Johnston NI, Gunasekharan VK, Ravindranath A, et al.Osteopontin as a target for cancertherapy. Front Biosci. 2008 May 1;13:4361-72.
[31]Zhu Y,Denhardt DT,Cao H,et al.Hypoxia upregulates osteopontin expression in NIH-3T3 cells via a Ras-activated enhancer[J].Oncogene,2005, 24(43):6555 -6563.
[32]宋前流,李学军.骨桥蛋白与肿瘤转移[J].医学分子生物学杂志,2005;2(1): 57-60
[33] Guo H, Marroquin CE, Wai PY,et al. Nitric oxide-dependent osteopontin expression induces metastatic behavior in HepG2 cells[J].Dig Dis Sci, 2005, 50(7): 1288-1298.
[34] Koopermann J, Fedarko NS, Jain A. et al. Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2004,13(3):487-91.
[35] Koprowski H, Steplewski Z, Mitchell K. et al.Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet.1979 ,5:957-972.
[36] Barone D, Onetto M, Conio M et al. CA 19-9 assays in patients with extrahepatic cholestatic jaundice. Int J Biol Markers.1988,3:95-100.
[37] Gabriel Sandblom, Sofie Granroth, Ib Christian Rasmussen, TPS, CA 19-9, VEGF-A, and CEA as Diagnostic and Prognostic Factors in Patients with Mass Lesions in the Pancreatic Head[J]. Upsala J Med Sci, 2008,113 (1): 57-64.
[1] Denhartdt DT, Guo X. Osteopontin:a protein with diverse functions [J].FASEB,1993,7 (15):1475.
[2] Lukaszewicz M, Mroczko B, Szmitkowski M. The role of metalloproteinases and their inhibitors in pancreatic cancer .Postepy Hig Med Dosw (Online). 2008 62(7):141-147.
[3] Rittling SR, Chambers AF. Role of osteopontin in tumour progression [J].Br J Cancer, 2004, 90(10):1877-1881.
[4] Senger DR, Wirth DF, Hynes RO.Transformed mammalian cells secrete specific proteins and phosphoproteins[J]. Cell .1979,16(4): 885-893.
[5] Weber GF. The metastasis gene osteopontin: a candidate target for cancer therapy [J]. Biochim iophysActa, 2001, 1552: 61-85.
[6] Gecilia MG, Susan Steitz. Mini review-Osteopontin: a versatile reulator of inflammation and biomineralization. Matrix Biol, 2000,19(7):615-622.
[7] Oldberg A,Franzen A,Heinegard D.Cloning and sequence analysis of rat bone sialoprotein (osteopontin)cDNA reveals an Arg-Gly-Asp cell-binding sequence.Proc Natl Acad Sci USA.1986 Dec;83(23):8819-8823.
[8] Butler WT.The nature and significance of osteopontin[J].Connect Tissue Res,1989,23 (2-3):123–136.
[9] Wai PY, Kuo PC. The role of osteopontin in tumor metastasis[J].J Surg Res,2004,121 (2): 228-241.
[10] Shapses SA, Cifuentes M, Spevak L, et al. Osteopontin facilitates bone resorption, decreasing bone mineral crystallinity and content during calcium deficiency·Calcif Tissue Int,2003,73(1):86-92.
[11] Tuck AB,HotaC,Wilson SM,et al.Osteopontin-induced migration of human mammary epithelial cells involves activation of EGF receptor and multiple signal transductionpathways. Oncogen ,2003,22(8):1198-1205.
[12] Ellen MG. Osteopontin: a bridge between bone and the immune system[J]. Clin Invest, 2003,112(2):147-149.
[13] Anthony WO,Gerard JN,Geoffrey LC,et al.Osteopontin(Eta-1) in cell-mediated immunity: Teaching an old dog new tricks[J].Immunology Today, 2000,21 (10):475-478.
[14] Lin YH,Yang Yen HF.The osteopontin CD44 survival signal involves activationof the phosphatidylinositol 3-kinase/Akt signaling pathway..J Biol Chem,2001, 276(49): 46024- 46030.
[15] Zhu Y, Denhardt DT, Cao H,et al.Hypoxia upregulates osteopontin expression in NIH- 3T3 cells via a Ras-activated enhancer[J].Oncogene,2005, 24(43):6555-6563.
[16] Marroquin CE, Downey L, Guo H.et al. Osteopontin increases CD44 expression and cell adhesion in RAW 264.7 murine leukemia cells. Immunol Lett. 2004 , 95(1):109-112.
[17] Chambers AF, Hota C, Prince CW. Adhesion of metastatic, ras-transformed NIH 3T3 cells to osteopontin, fibronectin, and laminin. Cancer Res, 1993, 53 (3): 701-706.
[18] Shijubo N, Uede T, Kon S,et al. Vascular endothelial growth factor and osteopontin in tumor biology. Crit Rev Oncog. 2000;11(2):135-46.
[19] Shijubo N, Uede T, Kon S, et al. Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma. Am J Respir Crit Care Med. 1999 Oct;160(4):1269-1273.
[20] Hirama M, Takahashi F, Takahashi K, et al. Osteopontin overproduced by tumor cells acts as a potent angiogenic factor contributing to tumor growth. Cancer Lett, 2003, 198 (1):107-117.
[21] Furge r KA,Allan AL,et al. Beta3 integrin expression increases breast carcinoma cell responsiveness to the malignaney-enhancing effeets of osteopontin[J].Mol Cancer Res, 2003,l(11):810-819.
[22]宋杏丽,李秉慧,韩梅等.骨桥蛋白诱导的黏着斑激酶信号途径参与大肠癌的侵袭与转移[J].中国老年学杂志,2005,25(9):1081-1083.
[23] Das R, Mahabeleshwar GH, Kundu GC. Osteopontin stimulates cell motility and nuclear factor kappaB-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells. J Biol Chem. 2003, 278(31): 28593-28606.
[24] Johnson GA, Burghardt RC, Joyce MM, et al. Osteopontin is synthesized by uterine glands and a 45-kDa cleavage fragment is localized at the uterine-placental interface throughout ovine pregnancy[J].Biol Reprod, 2003,69:92-98.
[25] Ariztia EV, Subbarao V, Solt DB,et al. Osteopontin contributes to hepatocyte growth factor-induced tumor growth and metastasis formation[J].Exp Cell Res, 2003, 288(2): 257-267.
[26] Zohar R,Suzuki N,Suzuki K, et al. Intracellular osteopontin is anintegral component of the CD44-ERM complex involved in cell migration [J].J Cell Physiol,2000,184(1):118- 130.
[27] Guo H, Marroquin CE, Wai PY,et al. Nitric oxide-dependent osteopontin expression induces metastatic behavior in HepG2 cells[J].Dig Dis Sci, 2005, 50(7): 1288-1298.
[28] Feng B, Rollo EE, Denhardt DT. Osteopontin (OPN) may facilitate metastasis by protecting cells from macrophage NO-mediated cytotoxicity: evidence from cell lines down-regulated for OPN expression by a targeted ribozyme. Clin Exp Metastasis. 1995, 13(6):453-462.
[29] Feng F, Rittling SR. Mammary tumor development in MMTV-c-myc/ MMTV-v-Ha-ras transgenic mice is unaffected by osteopontin deficiency. Breast Cancer Res Treat. 2000,63 (1):71-79.
[30] Maskos K, Bode W. Structural basis of matrix metalloproteinases and tissue inhibitors of metalloproteinases[J]. Mol Biotechnol,2003, 25(3):241-266.
[31] Ray JM, Stetler-Stevenson WG.The role of matrix metalloproteases and their inhibitors in tumour invasion ,metastasis and angiogenesis[J].Eur Respir J,1994,7(11):2062-2072.
[32] Koger M, Tschesche H. Cloning expression and action of a truncated 92Kda gelatinase minienzyme[J]. Gene, 1997,196:175-180.
[33] Breyholz HJ, Wagner S, Levkau B, et al. A (18)F-radiolabeled analogue of CGS 27023A as a potential agent for assessment of matrix-metalloproteinase activity in vivo[J]. Q J Nucl Med Mol Imaging, 2007,51(1):24-32.
[34] Laber TM,Balkwill FR.Regulation of monocyte MMP-9 production by TNF-a and a tumor-drived soluble fator(MMPSF).Br J Cancer,1998,78(6):724-732.
[35] Woessner JF.Matrix metalloproteinases and their inhibitors in connective tissue remodeling[J].FASEB J.1991,5(8):2145-2154.
[36] Liotta LA,Trygrason K,Garbisa S,et al.Metastatic potential correlates with enzymatic degradation of basement membrane collagen[J].Nature,1980,284:67.
[37]赵立阁,安瓦尼尔,祝诚.细胞外基质与基质蛋白酶[J].生物化学与生物物理进展,1999, 26(3):224-227.
[38] Noel A,Maillard C,Rocks N,et al.Membrane associated proteases and their inhibitors in tumour angiogenesis[J] Journal of Clinical Pathology.2004,57(6):577-584.
[39] Zucker S, Mirza H,Conner CE,et al.Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: conversion of proth- -rombin to thrombin results in progelatinase A activation and cell proliferation[J].Int J Cancer ,1998,75(5):780-786.
[40] Shin'ichi Miyamoto,Keiichi Yano,Seiji Sugimoto,et al.Matrix Metalloproteinase-7 Facilitates Insulin-Like Growth Factor Bioavailability through Its Proteinase Activity on Insulin-Like Growth Factor Binding Protein3.[J].Cancer Res,2004,64:665-671.
[41] Coppola D, SzaboM, Boulware D, et a.l Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin CancerRes, 2004, 10: 184-190.
[42]王维新,张国新,都波,等.骨桥蛋白、CD44v6在胰腺癌中的表达及其与临床病理特征的关系[J]南京医科大学学报(自然科学版)2007,27(8):801-803.
[43] Kolb A, Kleeff J, Guweidhi A, et al. Osteopontin Influences the Invasiveness of pan- -creatic cancer cells and is increased in neoplastic and inflammatory conditions [J].Cancer Biology and Therapy, 2005, 4(7): 740-746.
[44] Iacobuzio-Donahue CA,Maitra A, Shen-Ong GL, et al. Discovery of novel tumor markers of pancreatic cancer using global gene expression technology[J].Am J Pathol, 2002, 160 (4):1239-1249.
[45] Koopmann J, Fedarko NS, Jain A, et al. Evaluation of Osteopontin As biomarker for pancreatic adenocarcinoma[J].Cancer Epidemiol Biomarkers Prev, 2004, 13(3): 487-491.
[46] JonesL.E,CamPbell F,NeoptolemosJ.P,et al.Expression of matrix metalloproteinases- 2,3,7,8,9,12 and their tissue inhibitors (1,2 and 3) in panereatic adenocarcinoma.Br J Surg, 2000:87(5):676.
[47] Nagakawa Y, Aoki T, Kasuya K, et al. Histologic features of venous invasion, expression of vascular endothelial growth factor and matrix metalloproteinase-2 and matrix metalloproteinase-9, and relation with liver metastasis in pancreatic cancer. Pancreas,2002, 24: 169-178.
[48] Satoh K,Ohtani H,Shimosegawa T,et al. Infrequent stromal expression of gelatinase A and intact basement membrane in intraductal neoplasms of the Panereas. Gastroenterology. 1994:107:1488-1495.
[49] Bramhall SR,Neoptolemos JP,Stamp GW,et al. Imbalance of expression of matrix metalloproteinase(MMPs)and tissue inhipitors of the matrix metalloproteinase (TIMPS) in human pancreatic carcinoma[J]. J Pathol.1997,182(3):347-355.
[50] Gress TM,Muller-Pillaseh F,Lerch MM,et al.Expression and insitulocalization of genes coding for extracellular matrix proteins and extracellular matrix degrading protease:;in panereatic cancer.Int J Cancer1995;62:407-413.
[51] Kuniyasu H, Ellis LM, Evans DB, et al. Relative expression of E-cadherin and typeⅣcollagenases genes prsedicts outcome in patients with respectable pancreatic carcinoma. Clin Cancer Res,1999, 5: 25-33.
[52]Balaz Peter MD,Frieses,Helmut MD et al.Human Macrophage MetallolasesWorsens the Prognosis of pancreatic cancer.Ann Surg.2002;235(4):519-527.
[53]Weber GF, Zawaideh S,Hikita S, et a.l Phosphorylation-dependent interaction of osteo- -pontin with its receptors regulates macrophagemigration and activation[J]. J Leukoc Biol, 2002, 72(4):752-761.
[54]Rangaswami H, Bulbule A, Kundu GC. Nuclear factor inducing kinase plays a crucial role in osteopontin-induced MAPK/IKappaBalpha kinase-dependent nuclear factor kappaB-mediated promatrix metalloproteinase-9 activation [J]. J Biol Chem, 2004, 279 (37):38921-38935.
[55]Bodey B,Bodey JB,Siegel SE,et al.Prognostic significance of matrix metalloproteinase expression in colorectal carcinomas.In Vivo,2000,14:659-666.
[56]Jones JL,Walker RA. Control of martix metalloproteinase activity in cancer[J].J Pathol, 1997,183(4):377-379.
[57]Agrez M ,Gu X, Turton J,et al.The alpha v beta 6 integrin induces gelatinase B secretion in colon cancer cells. Int J Cancer 1999; 81(1): 90-97.
[58]Liu SJ,Hu GF,Liu YJ, et al.Effect of human osteopontin on proliferation, transmigration and expression of MMP-2 and MMP-9 in osteosarcoma cells. Chin Med J (Engl), 2004, 117(2): 235-240.
[59]张东涛,袁静,杨力,等.骨桥蛋白在胃癌中的表达及胃癌侵袭转移的关系[J].中华肿瘤杂志,2005,27(3):167-169.
[60] Jubo NS,Uede T,Kon S,et al. Vascular endothelial growth factor and osteopontin in stageⅠlung adenocarcinoma[J].Am J Respir Crit Care Med,1999,160(4):1269-1273.
[61]Lukacova S,Overgaard J, et al. Strain and tumour specific variations in the effete of hypoxia on osteopontin levels in experimental models [J]. Radiother Oncol,2006,80(2):165-171.
[62]Takahashi H, Sawai H, Funahashi H,et al. Antiproteases in preventing the invasive potential of pancreatic cancer cells. JOP. 2007 Jul 9;8(4 Suppl):501-508.
[63]Bloomston M, Zervos EE, Rosemurgy AS. Matrix metalloproteinases and their role in pancreatic cancer: a review of preclinical studies and clinical trials. Ann Surg Oncol. 2002,9(7):668-674.
[2]詹海勇,黄聪武,林銮群,等.血清糖链抗原19-9和糖链抗原242诊断胰腺癌的临床价值.疑难病杂志. 2006, 5(3):186.
[3] Wai PY, Kuo PC. The role of osteopontin in tumor metastasis. J Surg Res, 2004, 121(2): 228-241.
[4] Kolb A, Kleeff J, Guweidhi A, et al. Osteopontin influences the invasiveness of pancreatic cancer cells and is increased in neoplastic and inflammatory conditions. Cancer Biol Ther. 2005 Jul;4(7):740-746.
[5] Coppola D,Szabo M,Boulware D,et al.Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin Cancer Res. 2004;10(1 Pt 1):184-190.
[6] Nagase H. Activation mechanisms of matrix metalloproteinases. Biol Chem, 1997, 378:151-160.
[7] Shue JR, Fong TH, Liu CM, et al. Expression of matrix metalloproteinase-9 in human platelets regulation of platelet activation in vitro and in vivo studies[J]. Br J Pharmacol, 2004,143(1):193-201.
[8] Rooprai HK,vanMeter TE,Robinson SD,et a1.Expression of MMP2 and 9 in short-term Cultures of meningioma:influence of histological subtype[J].Int J Mol Med,2003,12(6): 977-981.
[9] Rangaswami H, Kundu GC. Osteopontin stimulates melanoma growth and lung metastasis through NIK/MEKK1-dependent MMP-9 activation pathways. Oncol Rep. 2007,18(4): 909-915.
[10]张东涛,袁静,杨力,等.骨桥蛋白在胃癌中的表达及胃癌侵袭转移的关系[J].中华肿瘤杂志,2005,27(3):167-169.
[11] Angelucci A,Festuccia C,Gravina GL,et al. osteopontin enhances the cell proliferation induced by the epidermal growth factor in human prostate cancer cells [J] Prostate,2004, 59(2):157.
[12] Kunigal S, Lakka SS, Joseph P, et al. Matrix metalloproteinase-9 inhibition down- regulates radiation-induced nuclear factor-kappa B activity leading to apoptosis in breast tumors. Clin Cancer Res. 2008 Jun 1;14(11):3617-3626.
[13] Lowenfels AB,Maisonneuve P.Epidemiology and prevention of pancreatic cancer,Jpn J Clin Oncol,2004,34:238-244.
[14] Urquidi V , Sloan D, Kawai K,et al. Contrasting expression of thrombospondin-1 and osteopontin correlates with absence or presence of metastatic phenotype in an isogenic model of spontaneous human breast cancer metastasis[J]. Clin Cancer Res, 2002,8:61-74.
[15] Senger DR, Wirth DF, Hynes RO.Transformed mammalian cells secrete specific proteins and phosphoproteins[J].Cell.1979,16(4): 885-893.
[16] Pryczynicz A, Guzińska-Ustymowicz K, Dymicka-Piekarska V, et al. Expression of matrix metalloproteinase 9 in pancreatic ductal carcinoma is associated with tumor metastasis formation[J]. Folia Histochem Cytobiol. 2007;45(1):37-40.
[17]王维新,张国新,都波,等,骨桥蛋白、CD44v6在胰腺癌中的表达及其与临床病理特征的关系[J]南京医科大学学报(自然科学版)2007,27(8):801-803.
[18] Sedivy R,Peters K,Kloppel G. Osteopontin expression in ductal adenocarcinomas and undifferentiated carcinomas of the pancreas.Virchows Arch. 2005;446(1):41-45.
[19] Weber GF, Zawaideh S,Hikita S, et a.l Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophagemigration and activation[J]. J Leukoc Biol, 2002, 72(4):752-761.
[20] Denhardt DT,Mistretta D,Chambers AF,et al.Transcriptional regulation of osteopontin and the metastatic phenotype:evidence for a Rasactivated enhancer in the human OPNpromoter〔J〕.Clin Exp Metastasis,2003,20(1):77.
[21] Giannopoulos G, Pavlakis K, Parasi A, et al. The expression of matrix metalloproteinases -2 and -9 and their tissue inhibitor 2 in pancreatic ductal and ampullary carcinoma and their relation to angiogenesis and clinicopathological parameters[J]. Anticancer Res. 2008,28(3B):1875-81.
[22] Furger KA,Allan AL,et al. Beta3 integrin expression increases breast carcinoma cell responsiveness to the malignaney-enhancing effeets of osteopontin[J].Mol Cancer Res. 2003,l(11):810-819.
[23] Jones JL,Walker RA. Control of martix metalloproteinase activity in cancer[J].J Pathol, 1997,183(4):377-379.
[24] Agrez M ,Gu X, Turton J,et al.The alpha v beta 6 integrin induces gelatinase B secretion in colon cancer cells. Int J Cancer 1999; 81(1): 90-97.
[25] Liu SJ, Hu GF, Liu YJ, et al. Effect of human osteopontin on proliferation, trans- -migration and expression of MMP-2 and MMP-9 in osteosarcoma cells. Chin Med J (Engl), 2004, 117(2): 235-240.
[26] Jubo NS,Uede T,Kon S,et al. Vascular endothelial growth factor and osteopontin in stageⅠlung adenocarcinoma[J].Am J Respir Crit Care Med,1999,160(4):1269-1273.
[27] Rangaswami H, Bulbule A, Kundu GC. Nuclear factor inducing kinase plays a crucial role in osteopontin-induced MAPK/IKappaBalpha kinase-dependent nuclear factor kappaB-mediated promatrix metalloproteinase-9 activation [J]. J Biol Chem, 2004, 279 (37):38921-38935.
[28]宋杏丽,李秉慧,韩梅等.骨桥蛋白诱导的黏着斑激酶信号途径参与大肠癌的侵袭与转移[J].中国老年学杂志,2005;25(9):1081-1083.
[29]杨力,张东涛,郭新宁.骨桥蛋白和核因子-KB在侵袭转移性胃癌中的表达[J].中国肿瘤临床,2004,31(16):901-903.
[30] Johnston NI, Gunasekharan VK, Ravindranath A, et al.Osteopontin as a target for cancertherapy. Front Biosci. 2008 May 1;13:4361-72.
[31]Zhu Y,Denhardt DT,Cao H,et al.Hypoxia upregulates osteopontin expression in NIH-3T3 cells via a Ras-activated enhancer[J].Oncogene,2005, 24(43):6555 -6563.
[32]宋前流,李学军.骨桥蛋白与肿瘤转移[J].医学分子生物学杂志,2005;2(1): 57-60
[33] Guo H, Marroquin CE, Wai PY,et al. Nitric oxide-dependent osteopontin expression induces metastatic behavior in HepG2 cells[J].Dig Dis Sci, 2005, 50(7): 1288-1298.
[34] Koopermann J, Fedarko NS, Jain A. et al. Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2004,13(3):487-91.
[35] Koprowski H, Steplewski Z, Mitchell K. et al.Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet.1979 ,5:957-972.
[36] Barone D, Onetto M, Conio M et al. CA 19-9 assays in patients with extrahepatic cholestatic jaundice. Int J Biol Markers.1988,3:95-100.
[37] Gabriel Sandblom, Sofie Granroth, Ib Christian Rasmussen, TPS, CA 19-9, VEGF-A, and CEA as Diagnostic and Prognostic Factors in Patients with Mass Lesions in the Pancreatic Head[J]. Upsala J Med Sci, 2008,113 (1): 57-64.
[1] Denhartdt DT, Guo X. Osteopontin:a protein with diverse functions [J].FASEB,1993,7 (15):1475.
[2] Lukaszewicz M, Mroczko B, Szmitkowski M. The role of metalloproteinases and their inhibitors in pancreatic cancer .Postepy Hig Med Dosw (Online). 2008 62(7):141-147.
[3] Rittling SR, Chambers AF. Role of osteopontin in tumour progression [J].Br J Cancer, 2004, 90(10):1877-1881.
[4] Senger DR, Wirth DF, Hynes RO.Transformed mammalian cells secrete specific proteins and phosphoproteins[J]. Cell .1979,16(4): 885-893.
[5] Weber GF. The metastasis gene osteopontin: a candidate target for cancer therapy [J]. Biochim iophysActa, 2001, 1552: 61-85.
[6] Gecilia MG, Susan Steitz. Mini review-Osteopontin: a versatile reulator of inflammation and biomineralization. Matrix Biol, 2000,19(7):615-622.
[7] Oldberg A,Franzen A,Heinegard D.Cloning and sequence analysis of rat bone sialoprotein (osteopontin)cDNA reveals an Arg-Gly-Asp cell-binding sequence.Proc Natl Acad Sci USA.1986 Dec;83(23):8819-8823.
[8] Butler WT.The nature and significance of osteopontin[J].Connect Tissue Res,1989,23 (2-3):123–136.
[9] Wai PY, Kuo PC. The role of osteopontin in tumor metastasis[J].J Surg Res,2004,121 (2): 228-241.
[10] Shapses SA, Cifuentes M, Spevak L, et al. Osteopontin facilitates bone resorption, decreasing bone mineral crystallinity and content during calcium deficiency·Calcif Tissue Int,2003,73(1):86-92.
[11] Tuck AB,HotaC,Wilson SM,et al.Osteopontin-induced migration of human mammary epithelial cells involves activation of EGF receptor and multiple signal transductionpathways. Oncogen ,2003,22(8):1198-1205.
[12] Ellen MG. Osteopontin: a bridge between bone and the immune system[J]. Clin Invest, 2003,112(2):147-149.
[13] Anthony WO,Gerard JN,Geoffrey LC,et al.Osteopontin(Eta-1) in cell-mediated immunity: Teaching an old dog new tricks[J].Immunology Today, 2000,21 (10):475-478.
[14] Lin YH,Yang Yen HF.The osteopontin CD44 survival signal involves activationof the phosphatidylinositol 3-kinase/Akt signaling pathway..J Biol Chem,2001, 276(49): 46024- 46030.
[15] Zhu Y, Denhardt DT, Cao H,et al.Hypoxia upregulates osteopontin expression in NIH- 3T3 cells via a Ras-activated enhancer[J].Oncogene,2005, 24(43):6555-6563.
[16] Marroquin CE, Downey L, Guo H.et al. Osteopontin increases CD44 expression and cell adhesion in RAW 264.7 murine leukemia cells. Immunol Lett. 2004 , 95(1):109-112.
[17] Chambers AF, Hota C, Prince CW. Adhesion of metastatic, ras-transformed NIH 3T3 cells to osteopontin, fibronectin, and laminin. Cancer Res, 1993, 53 (3): 701-706.
[18] Shijubo N, Uede T, Kon S,et al. Vascular endothelial growth factor and osteopontin in tumor biology. Crit Rev Oncog. 2000;11(2):135-46.
[19] Shijubo N, Uede T, Kon S, et al. Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma. Am J Respir Crit Care Med. 1999 Oct;160(4):1269-1273.
[20] Hirama M, Takahashi F, Takahashi K, et al. Osteopontin overproduced by tumor cells acts as a potent angiogenic factor contributing to tumor growth. Cancer Lett, 2003, 198 (1):107-117.
[21] Furge r KA,Allan AL,et al. Beta3 integrin expression increases breast carcinoma cell responsiveness to the malignaney-enhancing effeets of osteopontin[J].Mol Cancer Res, 2003,l(11):810-819.
[22]宋杏丽,李秉慧,韩梅等.骨桥蛋白诱导的黏着斑激酶信号途径参与大肠癌的侵袭与转移[J].中国老年学杂志,2005,25(9):1081-1083.
[23] Das R, Mahabeleshwar GH, Kundu GC. Osteopontin stimulates cell motility and nuclear factor kappaB-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells. J Biol Chem. 2003, 278(31): 28593-28606.
[24] Johnson GA, Burghardt RC, Joyce MM, et al. Osteopontin is synthesized by uterine glands and a 45-kDa cleavage fragment is localized at the uterine-placental interface throughout ovine pregnancy[J].Biol Reprod, 2003,69:92-98.
[25] Ariztia EV, Subbarao V, Solt DB,et al. Osteopontin contributes to hepatocyte growth factor-induced tumor growth and metastasis formation[J].Exp Cell Res, 2003, 288(2): 257-267.
[26] Zohar R,Suzuki N,Suzuki K, et al. Intracellular osteopontin is anintegral component of the CD44-ERM complex involved in cell migration [J].J Cell Physiol,2000,184(1):118- 130.
[27] Guo H, Marroquin CE, Wai PY,et al. Nitric oxide-dependent osteopontin expression induces metastatic behavior in HepG2 cells[J].Dig Dis Sci, 2005, 50(7): 1288-1298.
[28] Feng B, Rollo EE, Denhardt DT. Osteopontin (OPN) may facilitate metastasis by protecting cells from macrophage NO-mediated cytotoxicity: evidence from cell lines down-regulated for OPN expression by a targeted ribozyme. Clin Exp Metastasis. 1995, 13(6):453-462.
[29] Feng F, Rittling SR. Mammary tumor development in MMTV-c-myc/ MMTV-v-Ha-ras transgenic mice is unaffected by osteopontin deficiency. Breast Cancer Res Treat. 2000,63 (1):71-79.
[30] Maskos K, Bode W. Structural basis of matrix metalloproteinases and tissue inhibitors of metalloproteinases[J]. Mol Biotechnol,2003, 25(3):241-266.
[31] Ray JM, Stetler-Stevenson WG.The role of matrix metalloproteases and their inhibitors in tumour invasion ,metastasis and angiogenesis[J].Eur Respir J,1994,7(11):2062-2072.
[32] Koger M, Tschesche H. Cloning expression and action of a truncated 92Kda gelatinase minienzyme[J]. Gene, 1997,196:175-180.
[33] Breyholz HJ, Wagner S, Levkau B, et al. A (18)F-radiolabeled analogue of CGS 27023A as a potential agent for assessment of matrix-metalloproteinase activity in vivo[J]. Q J Nucl Med Mol Imaging, 2007,51(1):24-32.
[34] Laber TM,Balkwill FR.Regulation of monocyte MMP-9 production by TNF-a and a tumor-drived soluble fator(MMPSF).Br J Cancer,1998,78(6):724-732.
[35] Woessner JF.Matrix metalloproteinases and their inhibitors in connective tissue remodeling[J].FASEB J.1991,5(8):2145-2154.
[36] Liotta LA,Trygrason K,Garbisa S,et al.Metastatic potential correlates with enzymatic degradation of basement membrane collagen[J].Nature,1980,284:67.
[37]赵立阁,安瓦尼尔,祝诚.细胞外基质与基质蛋白酶[J].生物化学与生物物理进展,1999, 26(3):224-227.
[38] Noel A,Maillard C,Rocks N,et al.Membrane associated proteases and their inhibitors in tumour angiogenesis[J] Journal of Clinical Pathology.2004,57(6):577-584.
[39] Zucker S, Mirza H,Conner CE,et al.Vascular endothelial growth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: conversion of proth- -rombin to thrombin results in progelatinase A activation and cell proliferation[J].Int J Cancer ,1998,75(5):780-786.
[40] Shin'ichi Miyamoto,Keiichi Yano,Seiji Sugimoto,et al.Matrix Metalloproteinase-7 Facilitates Insulin-Like Growth Factor Bioavailability through Its Proteinase Activity on Insulin-Like Growth Factor Binding Protein3.[J].Cancer Res,2004,64:665-671.
[41] Coppola D, SzaboM, Boulware D, et a.l Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin CancerRes, 2004, 10: 184-190.
[42]王维新,张国新,都波,等.骨桥蛋白、CD44v6在胰腺癌中的表达及其与临床病理特征的关系[J]南京医科大学学报(自然科学版)2007,27(8):801-803.
[43] Kolb A, Kleeff J, Guweidhi A, et al. Osteopontin Influences the Invasiveness of pan- -creatic cancer cells and is increased in neoplastic and inflammatory conditions [J].Cancer Biology and Therapy, 2005, 4(7): 740-746.
[44] Iacobuzio-Donahue CA,Maitra A, Shen-Ong GL, et al. Discovery of novel tumor markers of pancreatic cancer using global gene expression technology[J].Am J Pathol, 2002, 160 (4):1239-1249.
[45] Koopmann J, Fedarko NS, Jain A, et al. Evaluation of Osteopontin As biomarker for pancreatic adenocarcinoma[J].Cancer Epidemiol Biomarkers Prev, 2004, 13(3): 487-491.
[46] JonesL.E,CamPbell F,NeoptolemosJ.P,et al.Expression of matrix metalloproteinases- 2,3,7,8,9,12 and their tissue inhibitors (1,2 and 3) in panereatic adenocarcinoma.Br J Surg, 2000:87(5):676.
[47] Nagakawa Y, Aoki T, Kasuya K, et al. Histologic features of venous invasion, expression of vascular endothelial growth factor and matrix metalloproteinase-2 and matrix metalloproteinase-9, and relation with liver metastasis in pancreatic cancer. Pancreas,2002, 24: 169-178.
[48] Satoh K,Ohtani H,Shimosegawa T,et al. Infrequent stromal expression of gelatinase A and intact basement membrane in intraductal neoplasms of the Panereas. Gastroenterology. 1994:107:1488-1495.
[49] Bramhall SR,Neoptolemos JP,Stamp GW,et al. Imbalance of expression of matrix metalloproteinase(MMPs)and tissue inhipitors of the matrix metalloproteinase (TIMPS) in human pancreatic carcinoma[J]. J Pathol.1997,182(3):347-355.
[50] Gress TM,Muller-Pillaseh F,Lerch MM,et al.Expression and insitulocalization of genes coding for extracellular matrix proteins and extracellular matrix degrading protease:;in panereatic cancer.Int J Cancer1995;62:407-413.
[51] Kuniyasu H, Ellis LM, Evans DB, et al. Relative expression of E-cadherin and typeⅣcollagenases genes prsedicts outcome in patients with respectable pancreatic carcinoma. Clin Cancer Res,1999, 5: 25-33.
[52]Balaz Peter MD,Frieses,Helmut MD et al.Human Macrophage MetallolasesWorsens the Prognosis of pancreatic cancer.Ann Surg.2002;235(4):519-527.
[53]Weber GF, Zawaideh S,Hikita S, et a.l Phosphorylation-dependent interaction of osteo- -pontin with its receptors regulates macrophagemigration and activation[J]. J Leukoc Biol, 2002, 72(4):752-761.
[54]Rangaswami H, Bulbule A, Kundu GC. Nuclear factor inducing kinase plays a crucial role in osteopontin-induced MAPK/IKappaBalpha kinase-dependent nuclear factor kappaB-mediated promatrix metalloproteinase-9 activation [J]. J Biol Chem, 2004, 279 (37):38921-38935.
[55]Bodey B,Bodey JB,Siegel SE,et al.Prognostic significance of matrix metalloproteinase expression in colorectal carcinomas.In Vivo,2000,14:659-666.
[56]Jones JL,Walker RA. Control of martix metalloproteinase activity in cancer[J].J Pathol, 1997,183(4):377-379.
[57]Agrez M ,Gu X, Turton J,et al.The alpha v beta 6 integrin induces gelatinase B secretion in colon cancer cells. Int J Cancer 1999; 81(1): 90-97.
[58]Liu SJ,Hu GF,Liu YJ, et al.Effect of human osteopontin on proliferation, transmigration and expression of MMP-2 and MMP-9 in osteosarcoma cells. Chin Med J (Engl), 2004, 117(2): 235-240.
[59]张东涛,袁静,杨力,等.骨桥蛋白在胃癌中的表达及胃癌侵袭转移的关系[J].中华肿瘤杂志,2005,27(3):167-169.
[60] Jubo NS,Uede T,Kon S,et al. Vascular endothelial growth factor and osteopontin in stageⅠlung adenocarcinoma[J].Am J Respir Crit Care Med,1999,160(4):1269-1273.
[61]Lukacova S,Overgaard J, et al. Strain and tumour specific variations in the effete of hypoxia on osteopontin levels in experimental models [J]. Radiother Oncol,2006,80(2):165-171.
[62]Takahashi H, Sawai H, Funahashi H,et al. Antiproteases in preventing the invasive potential of pancreatic cancer cells. JOP. 2007 Jul 9;8(4 Suppl):501-508.
[63]Bloomston M, Zervos EE, Rosemurgy AS. Matrix metalloproteinases and their role in pancreatic cancer: a review of preclinical studies and clinical trials. Ann Surg Oncol. 2002,9(7):668-674.