Cancer Res.:VEGF在肿瘤中的非促血管生成活性

据6月15日，Cancer Research杂志在线报道，血管内皮生长因子在肿瘤恶性进展过程中所发挥的不仅是促血管生成功能。

血管内皮生长因子/血管通透性因子（VEGF / VPF或VEGF-A）是肿瘤血管生成的关键驱动力，也是治疗恶性肿瘤的重要治疗靶点。然而，很少有研究工作涉及VEGF不依赖于其促血管生成活性的那部分功能。

该研究表明，由肿瘤细胞产生的血管内皮生长因子以自分泌方式，通过与血管内皮生长因子受体神经纤毛-1（NRP-1）的相互作用促进细胞生长。减少肿瘤细胞的血管内皮生长因子表达在体外可诱导分化表型，并在体内抑制肿瘤形成的能力。这些都以不依赖于促血管生成作用的方式完成。自分泌作用激活肿瘤细胞生长，依赖于NRP-1信号通路。而Ras被证实为NRP-1的一个重要的下游效应分子。

由此，该研究结果确定，在肿瘤细胞去分化过程中，血管内皮生长因子可发挥新功能，而不仅仅局限于其已知的促血管生成的功能。

doi:10.1016/j.cell.2011.10.017
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VEGF exerts an angiogenesis-independent function in cancer cells to promote their malignant progression

Ying Cao1, Guangqi E1, Enfeng Wang1, Krishnendu Pal1, Shamit K Dutta1, Dafna Bar-Sagi2, and Debabrata Mukhopadhyay1,*

Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF or VEGF-A) is a pivotal driver of cancer angiogenesis that is a central therapeutic target in treatment of malignancy. However, little work has been devoted to investigating functions of VEGF that are independent of its pro-angiogenic activity. Here we report that VEGF produced by tumor cells acts in an autocrine manner to promote cell growth through interaction with the VEGF receptor neuropilin-1 (NRP-1). Reducing VEGF expression by tumor cells induced a differentiated phenotype in vitro and inhibited tumor-forming capacity in vivo independent of effects on angiogenesis. Autocrine activation of tumor cell growth was dependent on signaling through NRP-1 and Ras was determined to a critical effector signaling molecule downstream of NRP-1. Our findings define a novel function for VEGF in de-differentiation of tumor cells, expanding its role in cancer beyond its known pro-angiogenic function.