Tie2 Expression on Macrophages Is Required for Blood Vessel Reconstruction and Tumor Relapse after Chemotherapy

被引：100

作者：

Chen, Lin ^{[1
,2
]}

Li, Jie ^{[1
,2
]}

Wang, Fei ^{[1
]}

Dai, Chengliang ^{[2
]}

Wu, Fan ^{[2
]}

Liu, Xiaoman ^{[2
]}

Li, Taotao ^{[3
]}

Glauben, Rainer ^{[4
]}

Zhang, Yi ^{[1
]}

Nie, Guangjun ^{[5
]}

He, Yulong ^{[3
]}

Qin, Zhihai ^{[1
,2
]}

机构：

[1] Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China

[2] Chinese Acad Sci, Inst Biophys, Key Lab Prot & Peptide Pharmaceut, Beijing, Peoples R China

[3] Soochow Univ, Lab Vasc & Canc Biol,Cyrus Tang Hematol Ctr, Collaborat Innovat Ctr Hematol,Jiangsu Key Lab Pr, Key Lab,Minist Hlth,Jiangsu Inst Hematol,Affiliat, Suzhou, Peoples R China

[4] Charite, Dept Med 1, Campus Benjamin Franklin, Berlin, Germany

[5] Natl Ctr Nanosci & Technol China, Beijing, Peoples R China

来源：

CANCER RESEARCH | 2016年 / 76卷 / 23期

基金：

中国国家自然科学基金;

关键词：

CELL-DEATH; ANGIOGENESIS; CANCER; RESISTANCE; MONOCYTES; VASCULOGENESIS; GLIOBLASTOMA; INFILTRATION; MECHANISMS; REJECTION;

D O I：

10.1158/0008-5472.CAN-16-1114

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C) 2016 AACR.

引用

页码：6828 / 6838

页数：11

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