@article{d9956eba2720474aa730e037d145f4b1,
title = "Targeting the ANG2/TIE2 Axis Inhibits Tumor Growth and Metastasis by Impairing Angiogenesis and Disabling Rebounds of Proangiogenic Myeloid Cells",
abstract = "Tumor-infiltrating myeloid cells convey proangiogenic programs that counteract the efficacy of antiangiogenic therapy. Here, we show that blocking angiopoietin-2 (ANG2), a TIE2 ligand and angiogenic factor expressed by activated endothelial cells (ECs), regresses the tumor vasculature and inhibits progression of late-stage, metastatic MMTV-PyMT mammary carcinomas and RIP1-Tag2 pancreatic insulinomas. ANG2 blockade did not inhibit recruitment of MRC1+ TIE2-expressing macrophages (TEMs) but impeded their upregulation of Tie2, association with blood vessels, and ability to restore angiogenesis in tumors. Conditional Tie2 gene knockdown in TEMs was sufficient to decrease tumor angiogenesis. Our findings support a model wherein the ANG2-TIE2 axis mediates cell-to-cell interactions between TEMs and ECs that are important for tumor angiogenesis and can be targeted to induce effective antitumor responses.",
author = "Roberta Mazzieri and Ferdinando Pucci and Davide Moi and Erika Zonari and Anna Ranghetti and Alvise Berti and Politi, {Letterio S.} and Bernhard Gentner and Brown, {Jeffrey L.} and Luigi Naldini and {De Palma}, Michele",
note = "Funding Information: We thank Francesca Sanvito and Martina Rocchi for help with pathology; Cesare Covino (ALEMBIC) for help with tumor imaging; Lucia Sergi Sergi for vector production; Giulia Escobar for help with some experiments; and ChingChing Leow (MedImmune, Gaithersburg, MD, USA) for helpful discussions. This research was supported by grants from the European Research Council (Starting Grant 243128/TIE2+Monocytes to M.D.P.; Advanced Grant 249845/TARGETINGGENETHERAPY to L.N.), the Associazione Italiana per la Ricerca sul Cancro (IG-2007 to L.N. and IG-2010 to M.D.P.), AstraZeneca (to L.N. and M.D.P), Fondazione Guido Berlucchi (to M.D.P.), and the Italian Ministry of Health “Challenge in Oncology” (to L.N.). E.Z. was supported by a FIRC fellowship. None of the authors has a financial interest related to this work. ",
year = "2011",
month = apr,
day = "12",
doi = "10.1016/j.ccr.2011.02.005",
language = "English (US)",
volume = "19",
pages = "512--526",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}