血管生成（Angiogenesis）是指從已有的毛細(xì)血管或毛細(xì)血管后靜脈發(fā)展而形成新的血管,，腫瘤血管生成的發(fā)生一方面是由于腫瘤細(xì)胞釋放血管生成因子激活血管內(nèi)皮細(xì)胞，促進(jìn)內(nèi)皮細(xì)胞的增殖和遷移,，另外一方面也是因?yàn)閮?nèi)皮細(xì)胞旁分泌某些血管生長(zhǎng)因子刺激腫瘤細(xì)胞的生長(zhǎng),。腫瘤細(xì)胞和內(nèi)皮細(xì)胞的相互作用自始至終貫穿于腫瘤血管生成的全過程。
通常,，腫瘤新生毛細(xì)血管是在原有的血管基礎(chǔ)上延伸擴(kuò)展而形成的,，其過程類似于典型的傷口愈合和胚胎形成過程。這些新生血管為不斷浸潤(rùn)生長(zhǎng)的原發(fā)腫瘤提供營(yíng)養(yǎng),，反過來,，腫瘤細(xì)胞在生長(zhǎng)過程中又分泌多種物質(zhì)以加速腫瘤新生毛細(xì)血管的形成。
越來越多的研究表明,，良性腫瘤血管生成稀少,，血管生長(zhǎng)緩慢；而大多數(shù)惡性腫瘤的血管生成密集且生長(zhǎng)迅速,。因此,，血管生成在腫瘤的發(fā)展轉(zhuǎn)移過程中起到重要作用，抑制這一過程將能明顯阻止腫瘤組織的發(fā)展和擴(kuò)散轉(zhuǎn)移,。
但最新研究再次證實(shí)用貝伐單抗抑制血管內(nèi)皮生長(zhǎng)因子信號(hào)結(jié)果導(dǎo)致膠質(zhì)母細(xì)胞瘤（GBM）小鼠模型以及GBM患者體內(nèi)的腫瘤細(xì)胞更具侵襲性,。相關(guān)研究論文發(fā)表在國(guó)際權(quán)威雜志Cancer cell上。研究數(shù)據(jù)表明血管內(nèi)皮生長(zhǎng)因子（VEGF）直接負(fù)調(diào)控腫瘤細(xì)胞的侵襲,，通過促進(jìn)蛋白酪氨酸磷酸酶1B（PTP1B）募集到間質(zhì)上皮轉(zhuǎn)化MET/VEGFR2雜合物中,，從而抑制肝細(xì)胞生長(zhǎng)因子依賴的MET磷酸化和腫瘤細(xì)胞遷移。
因此,，血管內(nèi)皮生長(zhǎng)因子的封閉抑制反而恢復(fù)和增加GBM細(xì)胞中MET的活性,。因此研究人員認(rèn)為在阻斷血管內(nèi)皮生長(zhǎng)因子時(shí)，同時(shí)抑制小鼠模型中腫瘤細(xì)胞的間質(zhì)轉(zhuǎn)型和侵襲將會(huì)大大提高導(dǎo)患者的生存時(shí)間,。（生物谷：Bioon.com）
doi:10.1016/j.ccr.2012.05.037
PMC:
PMID:
VEGF Inhibits Tumor Cell Invasion and Mesenchymal Transition through a MET/VEGFR2 Complex
Kan V. Lu, Jeffrey P. Chang, Christine A. Parachoniak, Melissa M. Pandika, Manish K. Aghi, David Meyronet, Nadezda Isachenko, Shaun D. Fouse, Joanna J. Phillips, David A. Cheresh, Morag Park, Gabriele Bergers
Inhibition of VEGF signaling leads to a proinvasive phenotype in mouse models of glioblastoma multiforme (GBM) and in a subset of GBM patients treated with bevacizumab. Here, we demonstrate that vascular endothelial growth factor (VEGF) directly and negatively regulates tumor cell invasion through enhanced recruitment of the protein tyrosine phosphatase 1B (PTP1B) to a MET/VEGFR2 heterocomplex, thereby suppressing HGF-dependent MET phosphorylation and tumor cell migration. Consequently, VEGF blockade restores and increases MET activity in GBM cells in a hypoxia-independent manner, while inducing a program reminiscent of epithelial-to-mesenchymal transition highlighted by a T-cadherin to N-cadherin switch and enhanced mesenchymal features. Inhibition of MET in GBM mouse models blocks mesenchymal transition and invasion provoked by VEGF ablation, resulting in substantial survival benefit.
