7月10日，Cancer Cell杂志以精选文章的形式报道了加州大学旧金山分校研究者关于血管内皮生长因子调节多形性胶质母细胞瘤间叶组织转变和侵袭性的最新研究进展。为人们进一步认识肿瘤的抗血管治疗，提供了新线索。
抑制血管内皮生长因子信号，可在多形性胶质母细胞瘤（GBM）的小鼠模型，以及某些贝伐单抗治疗的GBM患者中导致侵袭性增强的表型。
本研究表明，血管内皮生长因子（VEGF）通过加强招募蛋白酪氨酸磷酸酶1B（PTP1B）加入MET/VEGFR2杂合复合体，直接地对肿瘤细胞的侵袭性进行负调控。从而抑制肝细胞生长因子(HGF)依赖的间叶组织-表皮组织转变（MET）和肿瘤细胞迁移。
结果发现，血管内皮生长因子的阻断，以不依赖于缺氧的方式恢复和增加了GBM细胞内MET的活性，同时诱发细胞的T-cadherin转变为N-cadherin，和其他一些间叶组织特征增强的表型。在GBM小鼠模型中抑制MET可降低间叶组织转变和血管内皮生长因子阻断所引起的肿瘤细胞高侵袭性，对提高荷瘤小鼠的生存率大有益处。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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VEGF Inhibits Tumor Cell Invasionand Mesenchymal Transition through a MET/VEGFR2 Complex
Kan V. Lu,1,3 Jeffrey P. Chang,1,3 Christine A. Parachoniak,5,6 Melissa M. Pandika,1,3 Manish K. Aghi,1,3,4David Meyronet,1,3 Nadezda Isachenko,1,3 Shaun D. Fouse,1,3 Joanna J. Phillips,1,3,4 David A. Cheresh,7 Morag Park,5,6and Gabriele Bergers1,2,3,4,
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 vascularendothelial growth factor (VEGF) directly and negatively regulates tumor cell invasion through enhancedrecruitment of the protein tyrosine phosphatase 1B (PTP1B) to a MET/VEGFR2 heterocomplex, thereby sup-pressing HGF-dependent MET phosphorylation and tumor cell migration. Consequently, VEGF blockaderestores and increasesMET activity in GBM cells in a hypoxia-independentmanner,while inducing a programreminiscent of epithelial-to-mesenchymal transition highlighted by a T-cadherin to N-cadherin switch andenhanced mesenchymal features. Inhibition of MET in GBM mouse models blocks mesenchymal transitionand invasion provoked by VEGF ablation, resulting in substantial survival bene?t.
