Tie2 expression on macrophages is required for blood vessel reconstruction and tumor relapse after chemotherapy

Lin Chen, Jie Li, Fei Wang, Chengliang Dai, Fan Wu, Xiaoman Liu, Taotao Li, Rainer Glauben, Yi Zhang, Guangjun Nie, Yulong He, Zhihai Qin

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6828-6838
Number of pages11
JournalCancer research
Volume76
Issue number23
DOIs
StatePublished - Dec 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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