内皮细胞特异性分子-1在喉鳞状细胞癌组织中的表达及临床意义
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摘要
目的:
观察研究内皮细胞特异性分子-1(endocellular specific molecule-1,ESM-1)在喉癌组织中的表达及与临床病理特征的关系,探讨其表达改变在肿瘤发生、侵袭、转移中可能机制,为喉癌临床诊断、治疗提供依据。
方法:
采用免疫组织化学的方法对50例喉鳞癌及40例癌旁组织中ESM-1的表达进行检测,分析ESM-1的表达与喉癌临床病理特征的关系。同时收集20例新鲜喉癌及15例新鲜癌旁组织标本,采用Westernblot方法检测ESM-1的蛋白表达水平,运用RT-PCR方法检测ESM-1mRNA的表达水平。
结果:
免疫组织化学方法检测表明,喉鳞癌组织中ESM-1表达显著高于癌旁对照组织(P＜0.01);Ⅲ、Ⅳ期喉鳞癌组织中ESM-1的表达明显高于Ⅰ、Ⅱ期(P＜0.05);伴有颈淋巴结转移的喉鳞癌组织中ESM-1表达明显高于无淋巴结转移的标本(P＜0.05)。Western blot结果显示喉鳞癌组织中ESM-1蛋白表达明显高于癌旁组织,差别有统计学意义(P＜0.01);RT-PCR检测表明喉鳞癌中ESM-1 mRNA的表达明显高于喉癌旁组织,差别有统计学意义(P＜0.01)。
结论:
ESM-1在喉鳞癌组织中高表达,并且其表达程度与喉鳞癌的分期及是否存在淋巴结转移有关,提示ESM-1的表达与喉鳞癌的发生、侵袭、转移可能相关,可作为喉鳞癌预后判断的参考指标,并提供肿瘤干预治疗的靶点。
Objective:
To investigate the expression of human endocellular-specific molecule-1(ESM-1)in laryngeal carcinoma tissues and the relationship between ESM-1 expression and clinicopathological parameters,to study the action of ESM-1 in carcinogenesis,invasion and metastasis of tumor. Then look for a new target for diagnosis and treatment of laryngeal carcinoma
Methods:
The expression of ESM-1 in 50 specimens of laryngeal carcinoma and 40 specimens of para-carcinoma tissue was measured by the method of immunohistochemistry.The relationship between ESM-1 expression and clinicopathological parameters of laryngeal carcinoma was analyzed. Meanwhile,western blot was performed to detect the expression of ESM-1 in 20 fresh specimens of laryngeal carcinoma and 15 specimens of para-carcinoma tissue.Then RT-PCR was performed to detect ESM-1 mRNA expression.
Result:
The immunohistochemistry stain suggested that The qualitative expression of ESM-1 in laryngeal carcinoma tissues was significantly higher than that in para-carcinoma tissues(P＜0.01);it also has a higher expression inⅢ、Ⅳstage thanⅠ、Ⅱstage of laryngeal carcinoma.The positive expression of ESM-1 was also significantly correlated with carcinomatous metastasis.Western blot and RT-PCR also suggested that there was a higher expression of both mRNA and protein of ESM-1 in laryngeal carcinoma tissues than in para-carcinoma tissues(P＜0.01).
Conclusion:
In laryngeal carcinoma tissues,the expression of ESM-1 was higher than in para-carcinoma tissue and significantly related to metastasis and clinical stage,which may contribute to the carcinogenesis,development and invasion of laryngeal carcinoma.So ESM-1 may be an important index for judging prognosis of laryngeal carcinoma and provide a new target for cancer treatment.
观察研究内皮细胞特异性分子-1(endocellular specific molecule-1,ESM-1)在喉癌组织中的表达及与临床病理特征的关系,探讨其表达改变在肿瘤发生、侵袭、转移中可能机制,为喉癌临床诊断、治疗提供依据。
方法:
采用免疫组织化学的方法对50例喉鳞癌及40例癌旁组织中ESM-1的表达进行检测,分析ESM-1的表达与喉癌临床病理特征的关系。同时收集20例新鲜喉癌及15例新鲜癌旁组织标本,采用Westernblot方法检测ESM-1的蛋白表达水平,运用RT-PCR方法检测ESM-1mRNA的表达水平。
结果:
免疫组织化学方法检测表明,喉鳞癌组织中ESM-1表达显著高于癌旁对照组织(P＜0.01);Ⅲ、Ⅳ期喉鳞癌组织中ESM-1的表达明显高于Ⅰ、Ⅱ期(P＜0.05);伴有颈淋巴结转移的喉鳞癌组织中ESM-1表达明显高于无淋巴结转移的标本(P＜0.05)。Western blot结果显示喉鳞癌组织中ESM-1蛋白表达明显高于癌旁组织,差别有统计学意义(P＜0.01);RT-PCR检测表明喉鳞癌中ESM-1 mRNA的表达明显高于喉癌旁组织,差别有统计学意义(P＜0.01)。
结论:
ESM-1在喉鳞癌组织中高表达,并且其表达程度与喉鳞癌的分期及是否存在淋巴结转移有关,提示ESM-1的表达与喉鳞癌的发生、侵袭、转移可能相关,可作为喉鳞癌预后判断的参考指标,并提供肿瘤干预治疗的靶点。
Objective:
To investigate the expression of human endocellular-specific molecule-1(ESM-1)in laryngeal carcinoma tissues and the relationship between ESM-1 expression and clinicopathological parameters,to study the action of ESM-1 in carcinogenesis,invasion and metastasis of tumor. Then look for a new target for diagnosis and treatment of laryngeal carcinoma
Methods:
The expression of ESM-1 in 50 specimens of laryngeal carcinoma and 40 specimens of para-carcinoma tissue was measured by the method of immunohistochemistry.The relationship between ESM-1 expression and clinicopathological parameters of laryngeal carcinoma was analyzed. Meanwhile,western blot was performed to detect the expression of ESM-1 in 20 fresh specimens of laryngeal carcinoma and 15 specimens of para-carcinoma tissue.Then RT-PCR was performed to detect ESM-1 mRNA expression.
Result:
The immunohistochemistry stain suggested that The qualitative expression of ESM-1 in laryngeal carcinoma tissues was significantly higher than that in para-carcinoma tissues(P＜0.01);it also has a higher expression inⅢ、Ⅳstage thanⅠ、Ⅱstage of laryngeal carcinoma.The positive expression of ESM-1 was also significantly correlated with carcinomatous metastasis.Western blot and RT-PCR also suggested that there was a higher expression of both mRNA and protein of ESM-1 in laryngeal carcinoma tissues than in para-carcinoma tissues(P＜0.01).
Conclusion:
In laryngeal carcinoma tissues,the expression of ESM-1 was higher than in para-carcinoma tissue and significantly related to metastasis and clinical stage,which may contribute to the carcinogenesis,development and invasion of laryngeal carcinoma.So ESM-1 may be an important index for judging prognosis of laryngeal carcinoma and provide a new target for cancer treatment.
引文
1.田勇泉,孙爱华.耳鼻咽喉头颈外科学[M].北京:人民卫生出版社,2004年.216-220
2.Al-Mehdi AB,Tozawa K,FisherAB,et al.Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells:a new model for metastasis.NatMed 2000;6:100-2.
3.Hanahan D,Weinberg RA.The hallmarks of cancer.Cell 2000;100:57-70.
4.Tlsty TD,Coussens LM.Tumor stroma and regulation of cancer development.Ann Rev Pathol.Mech of Disease 2006;1:119-50.
5.Lassalle P,Molet S,Janin A et al.ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines,J.Biol.Chem.1996;271:20458-20464.
6.Bechard D,Gentina T,Delehedde M,et al.Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity.J Biol Chem 2001;276:48341-9.
7.熊江霞,吴强,周青,等.肾癌组织中内皮细胞特异性分子-1mRNA 水平及其蛋白表达的关系.临床与实验病理学杂志,2004,4:187-190.
8.董蕾,吴强,丁向东,等.涎腺腺样囊性癌中内皮细胞特异性分子-1、整合素β_1、的表达及临床意义.中国慢性病预防与控制.2007,15(6):236-238.
9.Aitkenhead M,Wang S.J,Nakatsu M.N,et al.Identification of endothelial cell genes expressed in an in vitro model of angiogenesis:induction of ESM-1,(beta)ig-h3,and NrCAM,Microvasc.Res.2002;63:159-171.
10.Scherpereel A,Gentina T,Grigoriu B,et al.Overexpression of endocan induces tumor formation,Cancer Res.2003;63:6084-6089.
11.Iozzo RV,San JD,Antonio.Heparan sulfate proteoglycans:heavy hitters in the angiogenesis arena,J.Clin.Invest.2001;108:349-355
12.Timar J,Lapis K,Dudas J et al.Proteoglycans and tumor progression:Janus-faced molecules with contradictory functions in cancer,Semin.Cancer Biol.2002;12:173-186
13.Sanderson RD,Yang Y,Suva LJ et al.Heparan sulfate proteoglycans and heparanase-Partners in osteolytic tumor growth and metastasis,Matrix Biol.2004;23:341-352.
14.Reed CC,Waterhouse A,Kirby Set al.Decorin prevents metastatic spreading of breast cancer,Oncogene 2005;24:1104-1110.
15.Grant DS,Yenisey C,Rose RW,Decorin suppresses tumor cell-mediated angiogenesis,Oncogene 2002;21:4765-4769
16.van't Veer LJ,Dai H,van deVijverMJ,et al.Gene expression profiling predicts clinical outcome of breast cancer.Nature 2002;415:530-6.
17.Borczuk AC,Shah L,Pearson GD,et al.Molecular signatures in biopsy specimens of lung cancer.Am J Respir Crit Care Med,2004,170:167-174.
18.刘卫卫,张淑君,韩广怀,等.内皮抑制素和血管内皮生长因子及碱性成纤维细胞生长因子-2在喉鳞状细胞癌中的表达及临床意义.中华耳鼻咽喉头颈外科杂志,2007,9:687-691.
19.Amatschek S,Koenig U,Auer H,et al.Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes.Cancer Res,2004,64:844-856.
20.Boldrini L,Calcinai A,SilvestriV,et al.Quantitation by competitive PCR assay of vascular endothelial growth factor in non-small cell lung carcinomas.Int J Oncol.1999;14:161-8.
1.Lassalle P,Molet S,Janin A et al.ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines,J.Biol.Chem.1996;271:20458-20464.
2.Scherpereel,Gentina T,Grigoriu B et al.Overexpression of ESM-1 induces tumor formation, Cancer Res. 2003; 63:6084- 6089.
3. Bechard D, Gentina T, Delehedde M et al. ESM-1 is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity, J. Biol. Chem. 2001; 276:48341- 48349.
4. Chen CY, Shyu AB. AU-rich elements: characterization and importance in mRNA degradation, Trends Biochem. Sci. 1995; 20:465-470.
5. Frevel MA, Bakheet T, Silva AM et al. p38 Mitogen-activated protein kinase-dependent and -independent signaling of mRNA stability of AU-rich element-containing transcripts, Mol. Cell. Biol. 2003; 23:425-436.
6. Tsai JC, Zhang J, Minami T et al. Cloning and characterization of the human lung endothelial-cell-specific molecule-1 promoter, J. Vasc. Res. 2002, 39:148-159.
7. Iozzo RV. Matrix proteoglycans: from molecular design to cellular function, Annu. Rev. Biochem. 1998; 67:609- 652.
8. Hai T, Hartman MG. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis, Gene 2001; 273:1-11.
9. Oikawa T, Yamada T. Molecular biology of the Ets family of transcription factors, Gene 2003; 303:11-34.
10. Aitkenhead M, Wang SJ, Nakatsu MN et al. Identification of endothelial cell genes expressed in an in vitromodel of angiogenesis: induction of ESM-1, (beta)ig-h3, and NrCAM, Microvasc. Res. 2002; 63:159-171.
11. Brinkman BM. Splice variants as cancer biomarkers, Clin. Biochem. 2004; 37:584-594.
12. Wellner M, Herse F, Janke J et al. Endothelial cell specific molecule-1—A newly identified protein in adipocytes, Horm. Metab. Res. 2003; 35:217-221.
13.Lassalle P, Molet S, Janin A et al. ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines, J. Biol. Chem. 1996; 271:20458-20464.
14. Gerritsen ME, Tomlinson JE, Zlot C et al. Using gene expression profiling to identify the molecular basis of the synergistic actions of hepatocyte growth factor and vascular endothelial growth factor in human endothelial cells, Br. J. Pharmacol. 2003; 140:595- 610.
15. Hendrix MJ, Seftor EA, Hess AR et al. Molecular plasticity of human melanoma cells, Oncogene 2003; 22:3070- 3075.
16. Iozzo RV, Cohen I. Altered proteoglycan gene expression and the tumor stroma, Experientia 1993; 49:447-455.
17. Iozzo RV, San Antonio JD. Heparan sulfate proteoglycans: heavy hitters in the angiogenesis arena, J. Clin. Invest. 2001; 108:349- 355.
18. Timar J, Lapis K, Dudas J et al. Proteoglycans and tumor progression: Janus-faced molecules with contradictory functions in cancer, Semin. Cancer Biol. 2002; 12:173-186.
19. Delehedde M. Heparan sulfate as a key player in the regulation of growth factor activities, Recent Res. Dev. Biol. Chem. 2002; 1:133-149.
20. Sanderson RD, Yang Y, Suva LJ et al. Heparan sulfate proteoglycans and heparanase—Partners in osteolytic tumor growth and metastasis, Matrix Biol. 2004; 23:341-352.
21. Delehedde M, Lortat-Jacob H, Gallagher JT et al. Proteoglycan involvement in inflammatory diseases. New developments in GAG-based therapies, Curr. Med. Chem. 2005; 2:345- 357.
22. Bechard D, Scherpereel A, Hammad H et al. Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18(LFA-1)and blocks binding to intercellular adhesion molecule-1,J.Immunol.2001;167:3099-3106.
23.Bechard D,Meignin V,Scherpereel A et al.Characterization of the secreted form of endothelial-cell-specific molecule 1 by specific monoclonal antibodies,J.Vasc.Res.2000;37:417-425.
24.Marshall JC.Such stuffs as dreams are made on:Mediator-directed therapy in sepsis.Nature Rev Drug Discovery 2003;2:391-40
25.刘景生主编.细胞信息与调控 北京医科大学中国协和医科大学出版社,第一版 1998;334-335
26.白柳惠图主编.细胞生物学 北京师范大学出版社 第二版 1998;426-431
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38. Grant DS, Yenisey C, Rose RW et al. Decorin suppresses tumor cell-mediated angiogenesis, Oncogene 2002; 21:4765
39. Scherpereel A, Gentina T, Grigoriu B et al. Overexpression of ESM-1 induces tumor formation, Cancer Res. 2003; 63:6084- 6089.
40. Grant DS, Yenisey C, Rose RW et al. Decorin suppresses tumor cell-mediated angiogenesis, Oncogene 2002; 21:4765- 4777.
41. Merle B, Durussel L, Delmas PD et al. Decorin inhibits cellmigration through a process requiring its glycosaminoglycan side chain, J. Cell. Biochem. 1999; 75:538-546.
42. De Lange MR, Davies C, Munn LL et al. Decorin inhibits endothelial migration and tube-like structure formation: role of thrombospondin-1, Microvasc. Res. 2001; 62:26-42.
43. Van 't Veer LJ, Dai H, Van de Vijver MJ et al. Gene expression profiling predicts clinical outcome of breast cancer, Nature 2002; 415:530-536.
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45. Amatschek S, Koenig U, Auer H et al. Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes, Cancer Res. 2004; 64:844-856.
2.Al-Mehdi AB,Tozawa K,FisherAB,et al.Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells:a new model for metastasis.NatMed 2000;6:100-2.
3.Hanahan D,Weinberg RA.The hallmarks of cancer.Cell 2000;100:57-70.
4.Tlsty TD,Coussens LM.Tumor stroma and regulation of cancer development.Ann Rev Pathol.Mech of Disease 2006;1:119-50.
5.Lassalle P,Molet S,Janin A et al.ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines,J.Biol.Chem.1996;271:20458-20464.
6.Bechard D,Gentina T,Delehedde M,et al.Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity.J Biol Chem 2001;276:48341-9.
7.熊江霞,吴强,周青,等.肾癌组织中内皮细胞特异性分子-1mRNA 水平及其蛋白表达的关系.临床与实验病理学杂志,2004,4:187-190.
8.董蕾,吴强,丁向东,等.涎腺腺样囊性癌中内皮细胞特异性分子-1、整合素β_1、的表达及临床意义.中国慢性病预防与控制.2007,15(6):236-238.
9.Aitkenhead M,Wang S.J,Nakatsu M.N,et al.Identification of endothelial cell genes expressed in an in vitro model of angiogenesis:induction of ESM-1,(beta)ig-h3,and NrCAM,Microvasc.Res.2002;63:159-171.
10.Scherpereel A,Gentina T,Grigoriu B,et al.Overexpression of endocan induces tumor formation,Cancer Res.2003;63:6084-6089.
11.Iozzo RV,San JD,Antonio.Heparan sulfate proteoglycans:heavy hitters in the angiogenesis arena,J.Clin.Invest.2001;108:349-355
12.Timar J,Lapis K,Dudas J et al.Proteoglycans and tumor progression:Janus-faced molecules with contradictory functions in cancer,Semin.Cancer Biol.2002;12:173-186
13.Sanderson RD,Yang Y,Suva LJ et al.Heparan sulfate proteoglycans and heparanase-Partners in osteolytic tumor growth and metastasis,Matrix Biol.2004;23:341-352.
14.Reed CC,Waterhouse A,Kirby Set al.Decorin prevents metastatic spreading of breast cancer,Oncogene 2005;24:1104-1110.
15.Grant DS,Yenisey C,Rose RW,Decorin suppresses tumor cell-mediated angiogenesis,Oncogene 2002;21:4765-4769
16.van't Veer LJ,Dai H,van deVijverMJ,et al.Gene expression profiling predicts clinical outcome of breast cancer.Nature 2002;415:530-6.
17.Borczuk AC,Shah L,Pearson GD,et al.Molecular signatures in biopsy specimens of lung cancer.Am J Respir Crit Care Med,2004,170:167-174.
18.刘卫卫,张淑君,韩广怀,等.内皮抑制素和血管内皮生长因子及碱性成纤维细胞生长因子-2在喉鳞状细胞癌中的表达及临床意义.中华耳鼻咽喉头颈外科杂志,2007,9:687-691.
19.Amatschek S,Koenig U,Auer H,et al.Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes.Cancer Res,2004,64:844-856.
20.Boldrini L,Calcinai A,SilvestriV,et al.Quantitation by competitive PCR assay of vascular endothelial growth factor in non-small cell lung carcinomas.Int J Oncol.1999;14:161-8.
1.Lassalle P,Molet S,Janin A et al.ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines,J.Biol.Chem.1996;271:20458-20464.
2.Scherpereel,Gentina T,Grigoriu B et al.Overexpression of ESM-1 induces tumor formation, Cancer Res. 2003; 63:6084- 6089.
3. Bechard D, Gentina T, Delehedde M et al. ESM-1 is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity, J. Biol. Chem. 2001; 276:48341- 48349.
4. Chen CY, Shyu AB. AU-rich elements: characterization and importance in mRNA degradation, Trends Biochem. Sci. 1995; 20:465-470.
5. Frevel MA, Bakheet T, Silva AM et al. p38 Mitogen-activated protein kinase-dependent and -independent signaling of mRNA stability of AU-rich element-containing transcripts, Mol. Cell. Biol. 2003; 23:425-436.
6. Tsai JC, Zhang J, Minami T et al. Cloning and characterization of the human lung endothelial-cell-specific molecule-1 promoter, J. Vasc. Res. 2002, 39:148-159.
7. Iozzo RV. Matrix proteoglycans: from molecular design to cellular function, Annu. Rev. Biochem. 1998; 67:609- 652.
8. Hai T, Hartman MG. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis, Gene 2001; 273:1-11.
9. Oikawa T, Yamada T. Molecular biology of the Ets family of transcription factors, Gene 2003; 303:11-34.
10. Aitkenhead M, Wang SJ, Nakatsu MN et al. Identification of endothelial cell genes expressed in an in vitromodel of angiogenesis: induction of ESM-1, (beta)ig-h3, and NrCAM, Microvasc. Res. 2002; 63:159-171.
11. Brinkman BM. Splice variants as cancer biomarkers, Clin. Biochem. 2004; 37:584-594.
12. Wellner M, Herse F, Janke J et al. Endothelial cell specific molecule-1—A newly identified protein in adipocytes, Horm. Metab. Res. 2003; 35:217-221.
13.Lassalle P, Molet S, Janin A et al. ESM-1 is a novel human endothelial cell-specific molecule expressed in lung and regulated by cytokines, J. Biol. Chem. 1996; 271:20458-20464.
14. Gerritsen ME, Tomlinson JE, Zlot C et al. Using gene expression profiling to identify the molecular basis of the synergistic actions of hepatocyte growth factor and vascular endothelial growth factor in human endothelial cells, Br. J. Pharmacol. 2003; 140:595- 610.
15. Hendrix MJ, Seftor EA, Hess AR et al. Molecular plasticity of human melanoma cells, Oncogene 2003; 22:3070- 3075.
16. Iozzo RV, Cohen I. Altered proteoglycan gene expression and the tumor stroma, Experientia 1993; 49:447-455.
17. Iozzo RV, San Antonio JD. Heparan sulfate proteoglycans: heavy hitters in the angiogenesis arena, J. Clin. Invest. 2001; 108:349- 355.
18. Timar J, Lapis K, Dudas J et al. Proteoglycans and tumor progression: Janus-faced molecules with contradictory functions in cancer, Semin. Cancer Biol. 2002; 12:173-186.
19. Delehedde M. Heparan sulfate as a key player in the regulation of growth factor activities, Recent Res. Dev. Biol. Chem. 2002; 1:133-149.
20. Sanderson RD, Yang Y, Suva LJ et al. Heparan sulfate proteoglycans and heparanase—Partners in osteolytic tumor growth and metastasis, Matrix Biol. 2004; 23:341-352.
21. Delehedde M, Lortat-Jacob H, Gallagher JT et al. Proteoglycan involvement in inflammatory diseases. New developments in GAG-based therapies, Curr. Med. Chem. 2005; 2:345- 357.
22. Bechard D, Scherpereel A, Hammad H et al. Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18(LFA-1)and blocks binding to intercellular adhesion molecule-1,J.Immunol.2001;167:3099-3106.
23.Bechard D,Meignin V,Scherpereel A et al.Characterization of the secreted form of endothelial-cell-specific molecule 1 by specific monoclonal antibodies,J.Vasc.Res.2000;37:417-425.
24.Marshall JC.Such stuffs as dreams are made on:Mediator-directed therapy in sepsis.Nature Rev Drug Discovery 2003;2:391-40
25.刘景生主编.细胞信息与调控 北京医科大学中国协和医科大学出版社,第一版 1998;334-335
26.白柳惠图主编.细胞生物学 北京师范大学出版社 第二版 1998;426-431
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