@article{3354f958024142f4a376242656213f74,
title = "Tie2 expression on macrophages is required for blood vessel reconstruction and tumor relapse after chemotherapy",
abstract = "Tumor relapse after chemotherapy is a major hurdle for successful cancer therapy. Chemotherapeutic drugs select for resistant tumor cells and reshape tumor microenvironment, including the blood supply system. Using animal models, we observed on macrophages in tumor tissue a close correlation between upregulated Tie2 expression and tumor relapse upon chemotherapy. Conditional deletion of Tie2 expression in macrophages significantly prohibited blood supply and regrowth of tumors. Tie2+ macrophages were derived from tumor-infiltrating Tie2- CD11b+ cells and hypoxia-induced Tie2 expression on these cells. Mechanistically, expression of Tie2 prevented macrophages from apoptosis in stress conditions via the AKT-dependent signaling pathway. Together, these results demonstrate that Tie2 expression by macrophages is necessary and sufficient to promote the reconstruction of blood vessels after chemotherapy, shedding new light on developing novel strategies to inhibit tumor relapse.",
author = "Lin Chen and Jie Li and Fei Wang and Chengliang Dai and Fan Wu and Xiaoman Liu and Taotao Li and Rainer Glauben and Yi Zhang and Guangjun Nie and Yulong He and Zhihai Qin",
note = "Funding Information: We would like to thank Dr. Naoki Mochizuki for generously providing us with Tie2-GFP plasmid; Qingyang Hu for programming for irrigated area quantification; Zhenzhen Wu for intracardially perfusion, Junying Jia and Zhenwei Yang for outstanding assistance with flow cytometry and real-time PCR; Qingcui Li, Ruirui Wang, and Yuan Wang for technical support; and Chen Ni and Yuqiao Sheng for helpful comments. This work was supported by the Ministry of Science and Technology of China (2012CB917103, 2016YFC1302305 to Z. Qin) and the National Natural Science Foundation of China (91229203, 81630068, 31670881 to Z. Qin). Y. He was supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Publisher Copyright: {\textcopyright}2016 AACR.",
year = "2016",
month = dec,
day = "1",
doi = "10.1158/0008-5472.CAN-16-1114",
language = "English (US)",
volume = "76",
pages = "6828--6838",
journal = "Cancer research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "23",
}