Integrin alpha v beta 3 as a therapeutic target for blocking tumor-induced angiogenesis

Abstract

The integrin receptor alphavbeta3 has been shown to play a critical role in several distinct processes, such as angiogenesis, osteoclast-mediated bone resorption and tumor metastasis. Its expression is upregulated in newly synthesized blood vessels produced in response to a variety of tumors and purified angiogenic factors. Studies show that alphavbeta3 is a critical target downstream from perhaps all angiogcnic factors. Proof-of-principle that alphavbeta3 antagonists such as monoclonal antibodies and small molecules block angiogenesis and tumor growth has been obtained in several animal models. Many endogenous inhibitors of angiogenesis such as angiostatin, endostatin and tumstatin seem to work through the alphavbeta3 receptor further emphasizing the critical role of this receptor in angiogenesis. In addition, the alphavbeta3 receptor has been clearly implicated in several pathological processes such as rheumatoid arthritis, osteoporosis, and metastasis of prostate cancer to bone. Thus alphavbeta3 may prove to be an important target for pharmacological intervention in more than one clinical setting.