Expression of Integrin αVβ3 in Pancreatic Carcinoma: Relation to MMP-2 Activation and Lymph Node Metastasis

Introduction Overexpression of integrin αVβ3 had been demonstrated in various tumors. Studies have suggested that elevated levels of integrin αVβ3 in melanoma cells are deeply involved in the mechanism of increased melanoma invasiveness. Aims To examine the expression of integrin αVβ3 in pancreatic carcinoma and to evaluate the correlation between integrin expression accompanied by MMP-2 activation and clinicopathologic factors. Methodology Integrin αVβ3 specific antibody LM-609 was used for immunochemical analysis, and intracellular localization was determined in human pancreatic cancer cell lines cultured on vitronectin coating. Fifty pancreatic adenocarcinomas analyzed immunohistochemically and 26 frozen samples were analyzed gelatin-zymographically. Results Two of three pancreatic cancer cell lines demonstrated integrin αVβ3 immunofluorescence with a membranous pattern, and 29 of 50 pancreatic carcinomas showed positive immunostaining of tumor cells. There was no significant correlation between integrin αVβ3 expression and tumor size, tumor grade, or peripancreatic invasion. However, primary tumors with lymph node metastasis featured significantly higher expression of integrin αVβ3 than those without node metastasis. Tumors with high integrin αVβ3 expression showed significantly higher MMP-2 activation ratios than did tumors with low expression. Conclusion Expression analysis in pancreatic cancer tissue demonstrated involvement of αVβ3 integrin in lymph node metastasis rather than peripancreatic invasion. MMP-2 activation is linked, at least in part, to the expression of integrin αVβ3 of pancreatic cancer cells.