CTGF inhibits cell motility and COX-2 expression in oral cancer cells

Jing-Yuan Chuang; Wan-Yu Yang; Chih-Ho Lai; Chia-Der Lin; Ming-Hsui Tsai; Chih-Hsin Tang

doi:10.1016/j.intimp.2011.02.008

CTGF inhibits cell motility and COX-2 expression in oral cancer cells

Int Immunopharmacol. 2011 Aug;11(8):948-54. doi: 10.1016/j.intimp.2011.02.008. Epub 2011 Feb 23.

Authors

Jing-Yuan Chuang¹, Wan-Yu Yang, Chih-Ho Lai, Chia-Der Lin, Ming-Hsui Tsai, Chih-Hsin Tang

Affiliation

¹ Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.

PMID: 21352962
DOI: 10.1016/j.intimp.2011.02.008

Abstract

Oral squamous cell carcinoma (SCC) has a striking tendency to migrate and metastasize. Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin synthase, has been implicated in tumor metastasis. Connective tissue growth factor (CTGF), a secreted protein that binds to integrins, modulates the invasive behavior of certain human cancer cells. However, the effect of CTGF on migration activity and COX-2 expression in human oral cells is mostly unknown. Here we found that CTGF reduced the migration and expression of COX-2 in human oral cancer cells. αvβ5 monoclonal antibody (mAb), phosphatidylinositol 3-kinase inhibitor (PI3K; Ly294002 and wortmannin) and Akt inhibitor reversed the CTGF-inhibited the migration and COX-2 down-regulation of oral cancer cells. CTGF stimulation decreased the phosphorylation of focal adhesion kinase (FAK), PI3K and Akt. In addition, c-Jun siRNA also antagonized the CTGF-inhibited migration and COX-2 expression. Moreover, CTGF decreased the binding of c-Jun to the AP-1 element on the COX-2 promoter. Taken together, our results indicated that CTGF inhibits the migration of oral cancer cells by decreasing COX-2 expression through the αvβ5 integrin receptor, FAK, PI3K, Akt, c-Jun and AP-1 signal transduction pathways.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Androstadienes / pharmacology
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / pharmacology
Cell Line, Tumor
Cell Movement / drug effects*
Chromones / pharmacology
Connective Tissue Growth Factor / antagonists & inhibitors
Connective Tissue Growth Factor / metabolism
Connective Tissue Growth Factor / pharmacology*
Cyclooxygenase 2 / biosynthesis*
Cyclooxygenase 2 / genetics
Down-Regulation
Focal Adhesion Kinase 1 / metabolism
Gene Expression Regulation, Neoplastic / drug effects
Genes, jun / genetics
Humans
Morpholines / pharmacology
Mouth Neoplasms / drug therapy
Mouth Neoplasms / genetics
Mouth Neoplasms / metabolism*
Mouth Neoplasms / pathology*
Phosphatidylinositol 3-Kinase / metabolism
Phosphoinositide-3 Kinase Inhibitors
Phosphorylation / drug effects
Promoter Regions, Genetic
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / administration & dosage
RNA, Small Interfering / genetics
Receptors, Vitronectin / immunology
Signal Transduction / drug effects
Transcription Factor AP-1 / metabolism
Wortmannin

Substances

Androstadienes
Antibodies, Monoclonal
CCN2 protein, human
Chromones
Morpholines
Phosphoinositide-3 Kinase Inhibitors
RNA, Small Interfering
Receptors, Vitronectin
Transcription Factor AP-1
integrin alphaVbeta5
Connective Tissue Growth Factor
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Cyclooxygenase 2
PTGS2 protein, human
Phosphatidylinositol 3-Kinase
Focal Adhesion Kinase 1
PTK2 protein, human
Proto-Oncogene Proteins c-akt
Wortmannin