000201570 001__ 201570
000201570 005__ 20181203023609.0
000201570 0247_ $$2doi$$a10.1016/j.celrep.2014.06.059
000201570 022__ $$a2211-1247
000201570 02470 $$2ISI$$a000341572200007
000201570 037__ $$aARTICLE
000201570 245__ $$aRole of angiopoietin-2 in adaptive tumor resistance to VEGF signaling blockade
000201570 269__ $$a2014
000201570 260__ $$aCambridge$$bElsevier$$c2014
000201570 300__ $$a11
000201570 336__ $$aJournal Articles
000201570 520__ $$aAngiopoietin-2 (ANG2/ANGPT2) is a context-dependent TIE2 receptor agonist/antagonist and proangiogenic factor. Although ANG2 neutralization improves tumor angiogenesis and growth inhibition by vascular endothelial growth factor (VEGF)-A signaling blockade, the mechanistic underpinnings of such therapeutic benefits remain poorly explored. We employed late-stage RIP1-Tag2 pancreatic neuroendocrine tumors (PNETs) and MMTV-PyMT mammary adenocarcinomas, which develop resistance to VEGF receptor 2 (VEGFR2) blockade. We found that VEGFR2 inhibition upregulated ANG2 and vascular TIE2 and enhanced infiltration by TIE2-expressing macrophages in the PNETs. Dual ANG2/VEGFR2 blockade suppressed revascularization and progression in most of the PNETs, whereas it had only minor additive effects in the mammary tumors, which did not upregulate ANG2 upon VEGFR2 inhibition. ANG2/VEGFR2 blockade did not elicit increased PNET invasion and metastasis, although it exacerbated tumor hypoxia and hematopoietic cell infiltration. These findings suggest that evasive tumor resistance to anti-VEGFA therapy may involve the adaptive enforcement of ANG2-TIE2 signaling, which can be reversed by ANG2 neutralization.
000201570 700__ $$aRigamonti, Nicolò
000201570 700__ $$0247463$$aKadioglu, Ece$$g214980
000201570 700__ $$0247058$$aKeklikoglou, Ioanna$$g187697
000201570 700__ $$aWyser Rmili, Céline
000201570 700__ $$aLeow, Ching Ching
000201570 700__ $$0246289$$aDe Palma, Michele$$g213145
000201570 773__ $$j8$$k3$$q696-706$$tCell reports
000201570 8564_ $$s5050929$$uhttps://infoscience.epfl.ch/record/201570/files/1-s2.0-S2211124714005610-main.pdf$$yPublisher's version$$zPublisher's version
000201570 909C0 $$0252421$$pUPDEPALMA$$xU12442
000201570 909CO $$ooai:infoscience.tind.io:201570$$pSV$$particle
000201570 917Z8 $$x182396
000201570 937__ $$aEPFL-ARTICLE-201570
000201570 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000201570 980__ $$aARTICLE