title: CCL5 promotes VEGF-dependent angiogenesis by down-regulating miR-200b through PI3K/Akt signaling pathway in human chondrosarcoma cells.
abstract: Chondrosarcoma is the second most common primary malignant bone cancer, with potential for local invasion and distant metastasis. Chemokine CCL5 (formerly RANTES) of the CC-chemokine family plays a crucial role in metastasis. Angiogenesis is essential for the cancer metastasis. However, correlation of CCL5 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma is still unknown. CCL5-mediated VEGF expression was assessed by qPCR, ELISA, and Western blotting. CCL5-induced angiogenesis was examined by migration and tube formation in endothelial progenitor cells in vitro. CCL5 increased VEGF expression and also promoted chondrosarcoma conditional medium-mediated angiogenesis in vitro and in vivo. Stimulation of chondrosarcoma with CCL5 augmented PI3K and Akt phosphorylation, while PI3K and Akt inhibitor or siRNA abolished CCL5-induced VEGF expression and angiogenesis. We also demonstrated CCL5 inhibiting miR-200b expression and miR-200b mimic reversing the CCL5-enhanced VEGF expression and angiogenesis. Moreover, in chondrosarcoma patients showed the positive correlation between CCL5 and VEGF; negative correlation between CCL5 and miR-200b. Taken together, results demonstrate CCL5 promoting VEGF-dependent angiogenesis in human chondrosarcoma cells by down-regulating miR-200b through PI3K/Akt signaling pathway.
authors.affiliation: Ph.D. Program for Aging, China Medical University, Taichung, Taiwan.
authors.forename: Guan-Ting
authors.initials: GT
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan. School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Hsien-Te
authors.initials: HT
authors.lastname: Chen
authors.affiliation: Functional Neurosurgery Division, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan. Department of Early Childhood Care and Education, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli County, Taiwan.
authors.forename: Hsi-Kai
authors.initials: HK
authors.lastname: Tsou
authors.affiliation: Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Tzu-Wei
authors.initials: TW
authors.lastname: Tan
authors.affiliation: Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan. School of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Fong
authors.affiliation: Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Po-Chen
authors.initials: PC
authors.lastname: Chen
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan. Department of Orthopedic Surgery, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan. Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan.
authors.forename: Wei-Hung
authors.initials: WH
authors.lastname: Yang
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Jui-Chieh
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Ph.D. Program for Aging, China Medical University, Taichung, Taiwan. Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan. Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D002642:Chick Embryo; D002813:Chondrosarcoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D049033:Chorioallantoic Membrane; D015536:Down-Regulation; D066026:Endothelial Progenitor Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt