title: Leptin increases VEGF expression and enhances angiogenesis in human chondrosarcoma cells.
abstract: BACKGROUND
  Leptin, 16kDa product of obese gene, is adipocytokine playing critical role in regulation of body weight. In recent years, leptin is also defined as potent angiogenic factor involving in tumorigenesis, angiogenesis, and metastasis. However, it is unknown whether leptin regulates VEGF production in human chondrosarcoma and contributing the tumor-associated angiogenesis.
  
  
  METHODS
  We analyzed protein level of leptin and VEGF in human chondrosarcoma tissues. Effects of leptin on chondrosarcoma cells were examined by in vitro and in vivo assays. In addition, intracellular signal pathways were investigated by pharmacological and genetic approaches.
  
  
  RESULTS
  We found that both leptin and VEGF are highly expressed in human chondrosarcoma tissues, and positively correlated with tumor stage. Leptin increases VEGF production by activating OBRl receptor and MAPKs (p38, ERK, and JNK), which in turn enhances binding of AP-1 transcription factor to VEGF promoter, resulting in the transactivation of VEGF expression and subsequently promoting migration and tube formation in endothelial progenitor cells (EPCs). In vivo, knockdown leptin significantly reduces angiogenesis and tumor growth.
  
  
  CONCLUSIONS
  Leptin may be a therapeutic target of angiogenesis and metastasis in chondrosarcoma.
  
  
  CONCLUSIONS
  These findings provide better understanding of pathogenesis of chondrosarcoma and can utilize this knowledge to design new therapeutic strategy.
authors.affiliation: Department of Orthopedic Surgery, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan; Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Wei-Hung
authors.initials: WH
authors.lastname: Yang
authors.affiliation: Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Jui-Chieh
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Kai-Hsiang
authors.initials: KH
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Chang-Hua Hospital, Ministry of Health and Welfare, Puhsin Township, Changhua County, Taiwan.
authors.forename: Shoou-Jyi
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan.
authors.forename: Yung-Sen
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan; Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan. Electronic address: chtang@mail.cmu.edu.tw.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
keywords: Chondrosarcoma; Endothelial progenitor cells; Leptin; Tumor angiogenesis; VEGF