Immunohistochemical analysis of integrin alpha vbeta3 expression on tumor-associated vessels of human carcinomas.
Expression of the alpha vbeta3 integrin is upregulated on sprouting endothelia. Systemic application of antibody or peptidic inhibitors of alpha vbeta3 function disrupts tumor angiogenesis and reduces growth and invasiveness of human tumors in animal models. We systematically investigated alpha vbeta3 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 vbeta3-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 vbeta3 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 vbeta3 expression. Remarkably, the vasculature in apparently normal tissue also stained for alpha vbeta3. However, the percentages of stained vessels and their staining intensity were lower than in neoplastic tissues. Besides the vascular alpha vbeta3 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 vbeta3-expressing vessels that could be targets for anti-alpha vbeta3-therapy.
Max
R
R
Department of Pathology, University Hospital Nijmegen, The Netherlands.
Gerritsen
R R
RR
Nooijen
P T
PT
Goodman
S L
SL
Sutter
A
A
Keilholz
U
U
Ruiter
D J
DJ
De Waal
R M
RM
D000230:Adenocarcinoma / Q000098:blood supply* / Q000473:pathology; D000911:Antibodies, Monoclonal; D001808:Blood Vessels / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D001940:Breast / Q000098:blood supply; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology; D003106:Colon / Q000098:blood supply; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply; D009336:Necrosis; D010179:Pancreas / Q000098:blood supply; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000473:pathology; D019030:Receptors, Vitronectin / Q000032:analysis / Q000096:biosynthesis*; D012016:Reference Values
D000911:Antibodies, Monoclonal; D019030:Receptors, Vitronectin