據(jù)6月15日,，Cancer Research雜志在線報(bào)道，血管內(nèi)皮生長因子在腫瘤惡性進(jìn)展過程中所發(fā)揮的不僅是促血管生成功能。
血管內(nèi)皮生長因子/血管通透性因子（VEGF / VPF或VEGF-A）是腫瘤血管生成的關(guān)鍵驅(qū)動(dòng)力,，也是治療惡性腫瘤的重要治療靶點(diǎn),。然而，很少有研究工作涉及VEGF不依賴于其促血管生成活性的那部分功能,。
該研究表明,，由腫瘤細(xì)胞產(chǎn)生的血管內(nèi)皮生長因子以自分泌方式，通過與血管內(nèi)皮生長因子受體神經(jīng)纖毛-1（NRP-1）的相互作用促進(jìn)細(xì)胞生長,。減少腫瘤細(xì)胞的血管內(nèi)皮生長因子表達(dá)在體外可誘導(dǎo)分化表型,，并在體內(nèi)抑制腫瘤形成的能力。這些都以不依賴于促血管生成作用的方式完成,。自分泌作用激活腫瘤細(xì)胞生長,，依賴于NRP-1信號(hào)通路。而Ras被證實(shí)為NRP-1的一個(gè)重要的下游效應(yīng)分子,。
由此,，該研究結(jié)果確定，在腫瘤細(xì)胞去分化過程中,，血管內(nèi)皮生長因子可發(fā)揮新功能,，而不僅僅局限于其已知的促血管生成的功能。(生物谷bioon.com)
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.
