IMMUNOHISTOCHEMICAL ANALYSIS OF INTEGRIN ALPHA-V-BETA-3 EXPRESSION ONTUMOR-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 o f alpha nu beta 3 function disrupts tumor angiogenesis and reduces gro wth and invasiveness of human tumors in animal models. We systematical ly investigated alpha nu beta 3 expression on tumor-associated vessels of 4 different human epithelial tumors and the corresponding normal t issues by means of immunohistochemistry on frozen sections using the a lpha nu beta 3-complex specific monoclonal antibody LM609. Variable le vels of LM609 staining were found in all carcinoma lesions. A consider able 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 a n increased alpha nu beta 3 expression. Remarkably, the vasculature in apparently normal tissue also stained for alpha nu beta 3. However, t he percentages of stained vessels and their staining intensity were lo wer than in neoplastic tissues. Besides the vascular alpha nu beta 3 e xpression, several extravascular cell types stained positive, in both normal and tumor specimens. Taken together, our findings show a consid erable number of colon, pancreas, lung and breast carcinoma lesions wi th many alpha nu beta 3-expressing vessels that could be targets for a nti-alpha nu beta-therapy. (C) 1997 Wiley-Liss, Inc.