Albany Medical College, Center for Cell Biology & Cancer Research, Albany, NY 12208, USA.
Expert Opin Ther Targets. 2011 Oct;15(10):1197-210. doi: 10.1517/14728222.2011.609557. Epub 2011 Aug 13.
Integrin receptors for cell adhesion to the extracellular matrix have important roles in all stages of cancer progression and metastasis. Since the integrin family was discovered in the early 1980's, many studies have identified critical adhesion and signaling functions for integrins expressed on tumor cells, endothelial cells and other cell types of the tumor microenvironment, in controlling proliferation, survival, migration and angiogenesis. In recent years, the laminin-binding integrin α3β1 has emerged as a potentially promising anti-cancer target on breast cancer cells.
Studies from the past decade that implicate integrins as promising anti-cancer targets and the development of integrin antagonists as anti-cancer therapeutics. Recent preclinical studies that have identified the laminin-binding integrin α3β1 as an appealing anti-cancer target and the knowledge gaps that must be closed to fully exploit this integrin as a therapeutic target for breast cancer.
Although the tumor-promoting functions of α3β1 implicate this integrin as a promising therapeutic target on breast cancer cells, successful exploitation of this integrin as an anti-cancer target will require a better understanding of the molecular mechanisms whereby it regulates specific tumor cell behaviors and the identification of the most appropriate α3β1 functions to antagonize on breast cancer cells.
细胞与细胞外基质黏附的整合素受体在癌症进展和转移的所有阶段都具有重要作用。自 20 世纪 80 年代初发现整合素家族以来,许多研究已经确定了肿瘤细胞、内皮细胞和肿瘤微环境中其他细胞类型上表达的整合素的关键黏附和信号转导功能,这些功能控制着增殖、存活、迁移和血管生成。近年来,层粘连蛋白结合整合素 α3β1 已成为乳腺癌细胞上一个有前途的潜在抗癌靶点。
过去十年的研究表明,整合素是有前途的抗癌靶点,整合素拮抗剂的开发是抗癌治疗的一种方法。最近的临床前研究已经确定层粘连蛋白结合整合素 α3β1 是一个有吸引力的抗癌靶点,以及为了充分利用这种整合素作为乳腺癌的治疗靶点,必须要解决的知识空白。
尽管 α3β1 的肿瘤促进功能将其作为乳腺癌细胞上有前途的治疗靶点,但成功利用这种整合素作为抗癌靶点将需要更好地了解它调节特定肿瘤细胞行为的分子机制,并确定在乳腺癌细胞上拮抗最适当的 α3β1 功能。