Kumar C Chandra
Department of Tumor Biology, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Curr Drug Targets. 2003 Feb;4(2):123-31. doi: 10.2174/1389450033346830.
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.
整联蛋白受体αvβ3已被证明在多个不同过程中发挥关键作用，如血管生成、破骨细胞介导的骨吸收和肿瘤转移。在响应多种肿瘤和纯化的血管生成因子而产生的新合成血管中，其表达上调。研究表明，αvβ3可能是所有血管生成因子下游的关键靶点。在多个动物模型中已获得原理证明，即αvβ3拮抗剂（如单克隆抗体和小分子）可阻断血管生成和肿瘤生长。许多内源性血管生成抑制剂，如血管抑素、内皮抑素和肿瘤抑素，似乎通过αvβ3受体发挥作用，这进一步强调了该受体在血管生成中的关键作用。此外，αvβ3受体显然与多种病理过程有关，如类风湿性关节炎、骨质疏松症以及前列腺癌向骨的转移。因此，αvβ3可能被证明是不止一种临床环境中药理学干预的重要靶点。
