title: CTGF promotes osteosarcoma angiogenesis by regulating miR-543/angiopoietin 2 signaling.
abstract: Osteosarcoma is the most common primary solid tumor of bone. It has a high metastatic potential and occurs predominantly in adolescents and young adults. Angiopoietin 2 (Angpt2) is a key regulator in tumor angiogenesis, facilitating tumor growth and metastasis. Connective tissue growth factor (CTGF, also known as CCN2), is a cysteine-rich protein that has been reported to promote metastasis of osteosarcoma. However, the effect of CTGF on Angpt2 regulation and angiogenesis in human osteosarcoma remains largely unknown. We found that overexpression of CTGF in osteosarcoma cells increased Angpt2 production and induced angiogenesis, in vitro and in vivo. Our findings demonstrate that CTGF-enhanced Angpt2 expression and angiogenesis is mediated by the phospholipase C (PLC)/protein kinase C (PKCδ) signaling pathway. Moreover, endogenous microRNA-543 (miR-543) expression was negatively regulated by CTGF via the PLC/PKCδ pathway. We also provide evidence showing clinical significance between CTGF, Angpt2, and miR-543 as well as tumor staging in human osteosarcoma tissue. CTGF may serve as a therapeutic target in the process of osteosarcoma metastasis and angiogenesis.
authors.affiliation: Department of Orthopedics, Dongyang People's Hospital, Wenzhou Medical University, Dongyang, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Wang
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Hsiao-Chi
authors.initials: HC
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Che
authors.initials: YC
authors.lastname: Cheng
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 Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
authors.forename: Yuan-Li
authors.initials: YL
authors.lastname: Huang
authors.affiliation: School of Medicine, China Medical University, Taichung, Taiwan; Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Department of Orthopedics, Dongyang People's Hospital, Wenzhou Medical University, Dongyang, China.
authors.forename: Guo-Hong
authors.initials: GH
authors.lastname: Xu
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 Orthopaedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan; Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan.
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Fong
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan. Electronic address: chtang@mail.cmu.edu.tw.
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D042702:Angiopoietin-2 / Q000235:genetics*; D000818:Animals; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000473:pathology; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction; D014162:Transfection
chemical_list: D042702:Angiopoietin-2; C577592:MIRN543 microRNA, human; D035683:MicroRNAs; D055513:Connective Tissue Growth Factor
keywords: Angiogenesis; Angiopoietin 2; CTGF; Osteosarcoma; miR-543