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

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          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. Cancer Res; 76(23); 6828-38. ©2016 AACR.

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          Author and article information

          Journal
          Cancer Res.
          Cancer research
          American Association for Cancer Research (AACR)
          1538-7445
          0008-5472
          Dec 01 2016
          : 76
          : 23
          Affiliations
          [1 ] The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
          [2 ] Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
          [3 ] Laboratory of Vascular and Cancer Biology, Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Thrombosis and Hemostasis Key Lab of the Ministry of Health, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, China.
          [4 ] Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Medical Department I, Berlin, Germany.
          [5 ] National Centre for Nanoscience and Technology of China, Beijing, China.
          [6 ] Laboratory of Vascular and Cancer Biology, Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases Thrombosis and Hemostasis Key Lab of the Ministry of Health, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, China. zhihai@ibp.ac.cn heyulong@suda.edu.cn.
          [7 ] The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China. zhihai@ibp.ac.cn heyulong@suda.edu.cn.
          Article
          0008-5472.CAN-16-1114
          10.1158/0008-5472.CAN-16-1114
          27758887
          ea35f015-e6aa-40a4-aee0-0bcea809be48
          History

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