CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma through integrin-dependent pathway

Huey En Tzeng, Jui Ching Chen, Chun Hao Tsai, Chien Chung Kuo, Horng Chaung Hsu, Wen Lee Hwang, Yi Chin Fong, Chih Hsin Tang

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34 Citations (Scopus)

Abstract

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. CCN3, also called nephroblastoma overexpressed gene (NOV), regulates proliferation and differentiation of cancer cells. However, the effect of CCN3 on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that CCN3 increased the migration and expression of matrix metalloproteinase (MMP)-13 in human chondrosarcoma cells (JJ012 cells). αvβ3 or αvβ5 monoclonal antibody (mAb), phosphatidylinositol 3-kinase (PI3K) inhibitors (Ly294002 and wortmannin) and Akt inhibitor inhibited the CCN3-induced increase of the migration and MMP-13 upregulation of chondrosarcoma cells. CCN3 stimulation increased the phosphorylation of focal adhesion kinase (FAK), PI3K, and Akt. In addition, NF-κB inhibitors also suppressed the cell migration and MMP-13 expression enhanced by CCN3. Moreover, CCN3 increased NF-κB luciferase activity and binding of p65 to the NF-κB element on the MMP-13 promoter. Taken together, our results indicate that CCN3 enhances the migration of chondrosarcoma cells by increasing MMP-13 expression through the αvβ3/αvβ5 integrin receptor, FAK, PI3K, Akt, p65, and NF-κB signal transduction pathway.

Original languageEnglish
Pages (from-to)3181-3189
Number of pages9
JournalJournal of Cellular Physiology
Volume226
Issue number12
DOIs
Publication statusPublished - Dec 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Tzeng, H. E., Chen, J. C., Tsai, C. H., Kuo, C. C., Hsu, H. C., Hwang, W. L., Fong, Y. C., & Tang, C. H. (2011). CCN3 increases cell motility and MMP-13 expression in human chondrosarcoma through integrin-dependent pathway. Journal of Cellular Physiology, 226(12), 3181-3189. https://doi.org/10.1002/jcp.22672