The Role of CTGF in Osteosarcoma Progression

골육종에서 CTGF의 발현과 발암기전에서의 역할

  • Han, Ilkyu (Department of Orthopaedic Surgery, Seoul National University Hospital) ;
  • Lee, Mi Ra (Department of Orthopaedic Surgery, Seoul National University Hospital) ;
  • Kim, Han-Soo (Department of Orthopaedic Surgery, Seoul National University Hospital)
  • 한일규 (서울대학교병원 정형외과) ;
  • 이미라 (서울대학교병원 정형외과) ;
  • 김한수 (서울대학교병원 정형외과)
  • Received : 2014.03.31
  • Accepted : 2014.06.04
  • Published : 2014.06.30


Purpose: To examine the expression of Connective Tissue Growth Factor (CTGF) in osteosarcoma and to evaluate its role in osteosarcoma invasion and proliferation. Materials and Methods: The mRNA expression of CTGF from 23 patient-derived osteosarcoma cell lines was examined, and the role of CTGF in cell invasion and proliferation was examined using siRNA transfection. Results: The over-expression of CTGF mRNA was observed in 17 cell lines (74%). CTGF-specific siRNA transfection into SaOS-2 and MG63 cell lines resulted in efficient knockdown of CTGF expression on Western blot analysis. siRNA transfected cells showed decreased migration on Matrigel invasion assay and decreased cell proliferation on WST-1 assay. Conclusion: These results indicated that the CTGF expression may play an important role in osteosarcoma progression, and may be a therapeutic target of osteosarcoma.


Supported by : 서울대학교병원


  1. Geller DS, Gorlick R. HER-2 targeted treatment of osteosarcoma: the challenges of developing targeted therapy and prognostic factors for rare malignancies. Expert Opin Pharmacother. 2010;11:51-61.
  2. Janeway KA, Barkauskas DA, Krailo MD, et al. Outcome for adolescent and young adult patients with osteosarcoma: a report from the Children's Oncology Group. Cancer. 2012;118:4597-605.
  3. Holbourn KP, Acharya KR, Perbal B. The CCN family of proteins: structure-function relationships. Trends Biochem Sci. 2008;33:461-73.
  4. Pan LH, Beppu T, Kurose A, et al. Neoplastic cells and proliferating endothelial cells express connective tissue growth factor (CTGF) in glioblastoma. Neurol Res. 2002;24:677-83.
  5. Dhar A, Ray A. The CCN family proteins in carcinogenesis. Exp Oncol. 2010;32:2-9.
  6. Lin MT, Kuo IH, Chang CC, et al. Involvement of hypoxiainducing factor-1alpha-dependent plasminogen activator inhibitor-1 up-regulation in Cyr61/CCN1-induced gastric cancer cell invasion. J Biol Chem. 2008;283:15807-15.
  7. Manara MC, Perbal B, Benini S, et al. The expression of ccn3(nov) gene in musculoskeletal tumors. Am J Pathol. 2002;160:849-59.
  8. Moritani NH, Kubota S, Sugahara T, Takigawa M. Comparable response of ccn1 with ccn2 genes upon arthritis: An in vitro evaluation with a human chondrocytic cell line stimulated by a set of cytokines. Cell Commun Signal. 2005;3:6.
  9. Xie D, Nakachi K, Wang H, Elashoff R, Koeffler HP. Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features. Cancer Res. 2001;61:8917-23.
  10. Chen PP, Li WJ, Wang Y, et al. Expression of Cyr61, CTGF, and WISP-1 correlates with clinical features of lung cancer. PLoS One. 2007;2:e534.
  11. Deng YZ, Chen PP, Wang Y, et al. Connective tissue growth factor is overexpressed in esophageal squamous cell carcinoma and promotes tumorigenicity through beta-catenin-T-cell factor/Lef signaling. J Biol Chem. 2007;282:36571-81.
  12. Clark JC, Akiyama T, Thomas DM, et al. RECK in osteosarcoma: a novel role in tumour vasculature and inhibition of tumorigenesis in an orthotopic model. Cancer. 2011;117:3517-28.
  13. Chen CC, Lau LF. Functions and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol. 2009;41:771-83.
  14. Kubota S, Takigawa M. CCN family proteins and angiogenesis: from embryo to adulthood. Angiogenesis. 2007;10:1-11.