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EMMPRIN regulates tumor growth and metastasis by recruiting bone marrow-derived cells through paracrine signaling of SDF-1 and VEGF
Authors:Yanke Chen  Xingchun Gou  Derek Kai Kong  Xiaofei Wang  Jianhui Wang  Zeming Chen  Chen Huang  Jiangbing Zhou
Institution:1. Experiment Center of Biomedical Research School of Medicine, Xi''an Jiaotong University, Xi''an 710061, P. R. China;2. Department of Neurosurgery, Yale University, New Haven, CT 06511, USA;3. Laboratory of Cell Biology and Translational Medicine, Xi''an Medical University, Xi''an 710021, P. R. China;4. Department of Pathology, Yale University, New Haven, CT 06511, USA;5. Department of Biomedical Engineering, Yale University, New Haven, CT 06510, USA
Abstract:EMMPRIN, a cell adhesion molecule highly expressed in a variety of tumors, is associated with poor prognosis in cancer patients. Mechanistically, EMMPRIN has been characterized to contribute to tumor development and progression by controlling the expression of MMPs and VEGF. In the present study, by using fluorescently labeled bone marrow-derived cells (BMDCs), we found that the down-regulation of EMMPRIN expression in cancer cells reduces tumor growth and metastasis, and is associated with the reduced recruitment of BMDCs. Further protein profiling studies suggest that EMMPRIN controls BMDC recruitment through regulating the secretion of soluble factors, notably, VEGF and SDF-1. We demonstrate that the expression and secretion of SDF-1 in tumor cells are regulated by EMMPRIN. This study reveals a novel mechanism by which EMMPRIN promotes tumor growth and metastasis by recruitment of BMDCs through controlling secretion and paracrine signaling of SDF-1 and VEGF.
Keywords:EMMPRIN  bone marrow-derived cells  SDF-1  VEGF  tumor growth and metastasis
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