Integrin αvβ3 as a Therapeutic Target for Blocking Tumor-Induced Angiogenesis

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Abstract
The integrin receptor αvβ3 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 αvβ3 is a critical target downstream from perhaps all angiogenic factors. Proof-of-principle that αvβ3 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 αvβ3 receptor further emphasizing the critical role of this receptor in angiogenesis. In addition, the αvβ3 receptor has been clearly implicated in several pathological processes such as rheumatoid arthritis, osteoporosis, and metastasis of prostate cancer to bone. Thus αvβ3 may prove to be an important target for pharmacological intervention in more than one clinical setting.

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