ANTIINTEGRIN ALPHA-V-BETA-3 BLOCKS HUMAN BREAST-CANCER GROWTH AND ANGIOGENESIS IN HUMAN SKIN

Angiogenesis plays a fundamental role in human breast tumor progressio n, In fact, recent findings indicate that vascular density is a progno stic indicator of breast cancer disease status, Evidence is presented that the integrin alpha v beta 3 is not only a marker of human breast tumor-associated blood vessels, but that it plays a significant role i n human angiogenesis and breast tumor growth. To assess the role of al pha v beta 3-dependent angiogenesis in the progression of human breast cancer, we examined a SCID mouse/human chimeric model with transplant ed full thickness human skin containing alpha v beta 3-negative human breast tumor cells, This tumor induced a human angiogenic response as measured by vascular cell immunoreactivity with monoclonal antibodies LM609 and P2B1 directed to human alpha v beta 3 and CD31, respectively , Intravenous administration of LM609 either prevented tumor growth or markedly reduced tumor cell proliferation within the microenvironment of the human skin, These LM609-treated tumors not only contained sign ificantly fewer human blood vessels but also appeared considerably les s invasive than tumors in control animals. These findings demonstrate that alpha v beta 3 antagonists may provide an effective antiangiogeni c approach for the treatment of human breast cancer.