Adhesion and Angiogenesis Laboratory, Institute of Cancer, Bart's and The London, Queen Mary's School of Medicine and Dentistry, London, United Kingdom.
PLoS One. 2010 Mar 22;5(3):e9766. doi: 10.1371/journal.pone.0009766.
Endothelial cell migration is an essential aspect of tumor angiogenesis. Rac1 activity is needed for cell migration in vitro implying a requirement for this molecule in angiogenesis in vivo. However, a precise role for Rac1 in tumor angiogenesis has never been addressed. Here we show that depletion of endothelial Rac1 expression in adult mice, unexpectedly, has no effect on tumor growth or tumor angiogenesis. In addition, repression of Rac1 expression does not inhibit VEGF-mediated angiogenesis in vivo or ex vivo, nor does it affect chemotactic migratory responses to VEGF in 3-dimensions. In contrast, the requirement for Rac1 in tumor growth and angiogenesis becomes important when endothelial beta3-integrin levels are reduced or absent: the enhanced tumor growth, tumor angiogenesis and VEGF-mediated responses in beta3-null mice are all Rac1-dependent. These data indicate that in the presence of alphavbeta3-integrin Rac1 is not required for tumor angiogenesis.
内皮细胞迁移是肿瘤血管生成的一个重要方面。 Rac1 的活性是体外细胞迁移所必需的，这意味着该分子在体内血管生成中是必需的。然而，Rac1 在肿瘤血管生成中的精确作用尚未得到解决。在这里，我们发现成年小鼠内皮 Rac1 表达的耗竭出乎意料地对肿瘤生长或肿瘤血管生成没有影响。此外，抑制 Rac1 表达并不抑制体内或体外 VEGF 介导的血管生成，也不影响 VEGF 在三维空间中的趋化性迁移反应。相比之下，当内皮细胞 β3 整合素水平降低或缺失时，Rac1 对肿瘤生长和血管生成的需求变得重要：β3 缺失小鼠中增强的肿瘤生长、肿瘤血管生成和 VEGF 介导的反应均依赖 Rac1。这些数据表明，在存在 alphavbeta3 整合素的情况下，Rac1 不是肿瘤血管生成所必需的。
