Immunohistochemical analysis of integrin alpha v beta 3 expression on tumor-associated vessels of human carcinomas

Expression of the alpha nu beta 3 integrin is upregulated on sprouting endothelia. Systemic application of antibody or peptidic inhibitors of alpha nu beta 3 function disrupts tumor angiogenesis and reduces growth and invasiveness of human tumors in animal models. We systematically investigated alpha nu beta 3 expression on tumor-associated vessels of 4 different human epithelial tumors and the corresponding normal tissues by means of immunohistochemistry on frozen sections using the alpha nu beta 3-complex specific monoclonal antibody LM609. Variable levels of LM609 staining were found in all carcinoma lesions. A considerable number of tumor tissues (35/50) expressed alpha nu beta 3 on more than 50% of their vessels. Inflammatory infiltrates and the possibly hypoxic conditions near necrotic areas of tumors were accompanied by an increased alpha nu beta 3 expression. Remarkably, the vasculature in apparently normal tissue also stained for alpha nu beta 3. However, the percentages of stained vessels and their staining intensity were lower than in neoplastic tissues. Besides the vascular alpha nu beta 3 expression, several extravascular cell types stained positive, in both normal and tumor specimens. Taken together, our findings show a considerable number of colon, pancreas, lung and breast carcinoma lesions with many alpha nu beta 3-expressing vessels that could be targets for anti-alpha nu beta-therapy. (C) 1997 Wiley-Liss, Inc.