食管癌高发区食管癌组织中VEGF,Angiopoietin及其受体的表达及意义

目的血管生成在肿瘤生长和转移中起重要作用。VEGF和Angiopoietin是目前已知特异性作用血管内皮细胞的促血管生成因子。本研究采用RNA酶保护性分析和免疫组织化学的方法对30例食管癌高发区食管癌的癌组织和癌旁组织VEGF,An-giopoietin及其受体的mRNA和蛋白表达水平进行检测。食管癌组织中VEGF及其受体Flt-1,淋巴内皮特异性受体Flt-4,Angiopoietin受体Tie-2以及血管内皮标志物CD31和CD105mRNA较其癌旁组织显著升高(P<0.05),Angiopoietin-1无显著变化。VEGF和An-giopoietin-1分别与其受体Flt-1和Tie-2mRNA上调具有显著的正相关(r分别为0.54和0.71,P<0.05),与CD31和CD105mRNA也具有显著的正相关(P<0.05)。免疫组织化学显示VEGF和Angiopoietin-2在食管癌组织中过度表达,提示食管癌组织中存在血管内皮和淋巴内皮的活跃增殖。联合抑制VEGF,Angiopoietin和淋巴内皮生长因子或其受体可能抑制肿瘤新生血管和淋巴管的形成,从而降低淋巴及血行转移的潜能。

Overexpression of VEGF, angiopoietin and their receptors in primary esophageal squamous cell carcinoma patients from a high incidence area in northern China

Objective Angiogenesis plays an important role in tumor growth and metastasis. VEGF and angiopoietin are the only growth factors proven to be specific and critical for blood vessel formation. We examined VEGF and its receptor fms-like tyrosine kinase (Flt)-1, VEGF-C receptor Flt-4 (which is lymphatic-specific receptor) , angiopoieitn-1 , angopoiet in-2 and theirreceptor Tie-2 mRNA and protein expressions in 30 primary esophageal squamous cell carcinomas patients from a high incidence area in northern China. The mRNA expressions of VEGF and its receptor Flt-1 , lymphatic-specific receptor Flt-4, angiopoietin receptor Tie-2, CD31 and CD105 were significantly increased in cancers as compared to paired adjacent non-cancerous tissues (P <0.05) determined by multiprobe RNase protection assay, while the increase in angiopoietin-1 was not significant. The up-regulation of both VEGF and angiopoietin-1 mRNA had significant correlation with its receptor Flt-1 and Tie-2,respectively, and with both CD31 and CD105 as well. The overexpression of VEGF and angiopoieitn-2 proteins were confirmed by immunohistochemistry staining. These findings suggested that VEGF and angiopoietin are important angiogenic factors in primary esophageal carcinoma, the vascular and lymphatic angiogenesis may potentiate the metastatic potential.