7月10日，Cancer Cell雜志以精選文章的形式報道了加州大學舊金山分校研究者關于血管內皮生長因子調節(jié)多形性膠質母細胞瘤間葉組織轉變和侵襲性的最新研究進展,。為人們進一步認識腫瘤的抗血管治療，提供了新線索,。
抑制血管內皮生長因子信號，可在多形性膠質母細胞瘤（GBM）的小鼠模型,，以及某些貝伐單抗治療的GBM患者中導致侵襲性增強的表型,。
本研究表明，血管內皮生長因子（VEGF）通過加強招募蛋白酪氨酸磷酸酶1B（PTP1B）加入MET/VEGFR2雜合復合體,，直接地對腫瘤細胞的侵襲性進行負調控,。從而抑制肝細胞生長因子(HGF)依賴的間葉組織-表皮組織轉變（MET）和腫瘤細胞遷移。
結果發(fā)現(xiàn),，血管內皮生長因子的阻斷,，以不依賴于缺氧的方式恢復和增加了GBM細胞內MET的活性，同時誘發(fā)細胞的T-cadherin轉變?yōu)镹-cadherin,，和其他一些間葉組織特征增強的表型,。在GBM小鼠模型中抑制MET可降低間葉組織轉變和血管內皮生長因子阻斷所引起的腫瘤細胞高侵襲性，對提高荷瘤小鼠的生存率大有益處,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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PMID:
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.
