Non-angiogenic functions of VEGF in breast cancer
Non-angiogenic functions of VEGF in breast cancer
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DOI：
10.1007/s10911-006-9001-9
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发表时间：
2005-10-01
影响因子：
2.5
通讯作者：
Bachelder, Robin E.
中科院分区：
文献类型：
--
作者：
Mercurio, Arthur M.;Lipscomb, Elizabeth A.;Bachelder, Robin E.
本文提出的假设是，血管内皮生长因子在乳腺癌中的作用不仅限于血管生成，而且乳腺癌细胞中的血管内皮生长因子信号对这些细胞逃避凋亡和发展为侵袭性和转移性疾病的能力是重要的。换句话说，血管内皮生长因子信号为乳腺癌细胞的存活和扩散提供了选择性优势，这种优势可能不依赖于血管生成。这一假说的关键组成部分是乳腺癌细胞表达特定的血管内皮生长因子受体，这些受体对自分泌的血管内皮生长因子产生反应，导致信号通路的激活，从而阻碍细胞凋亡和促进细胞迁移。本文提出的一个相关假设是，与乳腺癌细胞的存活和运动有关的α-6-β-4整合素可以刺激血管内皮生长因子信使核糖核酸的翻译，从而自分泌血管内皮生长因子信号。这些发现表明，基于血管内皮生长因子和血管内皮生长因子受体的治疗药物，除了以血管生成为靶点外，还可能直接针对肿瘤细胞。
This review advances the hypothesis that the function of vascular endothelial growth factor (VEGF) in breast cancer is not limited to angiogenesis, and that VEGF signaling in breast carcinoma cells is important for the ability of these cells to evade apoptosis and progress towards invasive and metastatic disease. In other terms, VEGF signaling provides a selective advantage for the survival and dissemination of breast carcinoma cells that may be independent of angiogenesis. The key component of this hypothesis is that breast carcinoma cells express specific VEGF receptors and that these receptors respond to autocrine VEGF, resulting in the activation of signaling pathways that impede apoptosis and promote cell migration. A related hypothesis, which is developed in this review, is that the alpha 6 beta 4 integrin, which has been implicated in the survival and motility of breast cancer cells, can stimulate the translation of VEGF mRNA and, consequently, autocrine VEGF signaling. These findings imply that VEGF and VEGF receptor-based therapeutics, in addition to targeting angiogenesis, may also target tumor cells directly.