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. Cancer Res; 76(23); 6828-38. ©2016 AACR.
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.|Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.|Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Chengliang
authors.initials: C
authors.lastname: Dai
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Taotao
authors.initials: T
authors.lastname: Li
authors.affiliation: Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Medical Department I, Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Glauben
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Centre for Nanoscience and Technology of China, Beijing, China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Nie
authors.affiliation: 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.
authors.forename: Yulong
authors.initials: Y
authors.lastname: He
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China. zhihai@ibp.ac.cn heyulong@suda.edu.cn.|Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
mesh_terms: D000818:Animals; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D042787:Receptor, TIE-2 / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D042787:Receptor, TIE-2