7月10日，Cancer Cell雜志以精選文章的形式報(bào)道了加州大學(xué)舊金山分校研究者關(guān)于血管內(nèi)皮生長(zhǎng)因子調(diào)節(jié)多形性膠質(zhì)母細(xì)胞瘤間葉組織轉(zhuǎn)變和侵襲性的最新研究進(jìn)展。為人們進(jìn)一步認(rèn)識(shí)腫瘤的抗血管治療，提供了新線索。
抑制血管內(nèi)皮生長(zhǎng)因子信號(hào),，可在多形性膠質(zhì)母細(xì)胞瘤（GBM）的小鼠模型，以及某些貝伐單抗治療的GBM患者中導(dǎo)致侵襲性增強(qiáng)的表型。
本研究表明,，血管內(nèi)皮生長(zhǎng)因子（VEGF）通過(guò)加強(qiáng)招募蛋白酪氨酸磷酸酶1B（PTP1B）加入MET/VEGFR2雜合復(fù)合體，直接地對(duì)腫瘤細(xì)胞的侵襲性進(jìn)行負(fù)調(diào)控,。從而抑制肝細(xì)胞生長(zhǎng)因子(HGF)依賴的間葉組織-表皮組織轉(zhuǎn)變（MET）和腫瘤細(xì)胞遷移,。
結(jié)果發(fā)現(xiàn),，血管內(nèi)皮生長(zhǎng)因子的阻斷，以不依賴于缺氧的方式恢復(fù)和增加了GBM細(xì)胞內(nèi)MET的活性,，同時(shí)誘發(fā)細(xì)胞的T-cadherin轉(zhuǎn)變?yōu)镹-cadherin,，和其他一些間葉組織特征增強(qiáng)的表型。在GBM小鼠模型中抑制MET可降低間葉組織轉(zhuǎn)變和血管內(nèi)皮生長(zhǎng)因子阻斷所引起的腫瘤細(xì)胞高侵襲性,，對(duì)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.
