MMP-2、VEGF在食管癌变过程中的作用研究

Roles of MMP-2 and VEGF expressions in activated stromal fibroblasts during esophageal carcinogenesis

目的研究活化的间质成纤维细胞表达的基质金属蛋白酶2(MMP-2)及血管内皮生长因子(VEGF)蛋白在正常食管、食管癌前病变、早期食管癌、进展期食管癌发展过程中的作用。方法免疫组织化学法检测MMP-2和VEGF蛋白在正常食管20例,低级别上皮内瘤变30例,高级别上皮内瘤变50例,早期癌25癌,进展期癌25例中的表达。抗体CD34标记血管内皮细胞,检测微血管密度。结果随食管癌变进展,MMP-2蛋白在食管间质中的表达阳性率依次为0%(0/20)、0%(0/30)、28%(14/50)、40%(10/25)和60%(15/25)。VEGF蛋白在间质成纤维细胞中的表达阳性率依次为0%(0/20)、3%(1/30)、26%(13/50)、36%(9/25)和52%(13/25),MMP-2和VEGF蛋白在5组比较,差异有统计学意义(P<0.05)。结论随着食管癌变进展,间质成纤维细胞发生活化,分泌表达的MMP-2逐渐增多,从而降解基底膜,促进癌的下侵;过度表达的VEGF蛋白促进间质微血管的形成,加速癌的进展和转移。

Objective To investigate the expressions of matrix metalloproteinase 2(MMP-2) and vascular endothelial growth factor(VEGF) proteins in the stromal fibroblasts in different esophageal lesions from normal tissue, precancerous lesion, to early carcinoma(CIS) and advanced carcinoma(EA). Methods IHC method was uesd to detect the expression of MMP-2 protein and VEGF protein in the stromal fibroblasts and epithelia in different lesions in esophageal carcinogenesis, including normal group(20 cases), low-grade intraepithelial neoplasia(LGIEN) group(30 cases), HGIEN group(50 cases), CIS group(25 cases) and EA group(25 cases)respectively. Antibody CD34 was used to label vascular endothelial cells for microvascular density detection.Results In the esophageal stromal fibroblasts of the normal, LGIEN, HGIEN, CIS and EA groups, the positive-expression rates of MMP-2 protein were 0%(0/20), 0%(0/30), 28%(14/50), 40%(10/25) and 60%(15/25) respectively; and the positive-expression rates of VEGF protein were 0.0%(0/20), 3.3%(1/30), 26.0%(13/50), 36.0%(9/25) and 52.0%(13/25) respectively. The positive expression rates of each protein had significant differences among the five groups(P < 0.05). Conclusions With esophageal cancer progression, the interstitial fibroblasts are activated, the secretion of MMP-2 protrein increases, resulting in degradation of the basement membrane and promotion of cancer invasion. Excessive expression of VEGF protein promotes the formation of interstitial capillaries, accelerates cancer progression and metastasis.