Osteopontin increases migration and MMP-9 up-regulation via alphavbeta3 integrin, FAK, ERK, and NF-kappaB-dependent pathway in human chondrosarcoma cells.
Tumor malignancy is associated with several features such as proliferation ability and frequency of metastasis. Osteopontin (OPN), which abundantly expressed in bone matrix, is involved in cell adhesion, migration, invasion and proliferation via interaction with its receptor, that is, alphavbeta3 integrin. However, the effect of OPN on migration activity in human chondrosarcoma cells is mostly unknown. Here we found that OPN increased the migration and expression of matrix metalloproteinase (MMP)-9 in human chondrosarcoma cells (JJ012 cells). RGD peptide, alphavbeta3 monoclonal antibody and MAPK kinase (MEK) inhibitors (PD98059 and U0126) but not RAD peptide inhibited the OPN-induced increase of the migration and MMP-9 up-regulation of chondrosarcoma cells. OPN stimulation increased the phosphorylation of focal adhesion kinase (FAK), MEK and extracellular signal-regulated kinase (ERK). In addition, treatment of JJ012 cells with NF-kappaB inhibitor (PDTC) or IkappaB protease inhibitor (TPCK) inhibited OPN-induced cell migration and MMP-9 up-regulation. Stimulation of JJ012 cells with OPN also induced IkappaB kinase alpha/beta (IKK alpha/beta) phosphorylation, IkappaBalpha phosphorylation, p65 Ser(536) phosphorylation, and kappaB-luciferase activity. The OPN-mediated increases in MMP-9 and kappaB-luciferase activities were inhibited by RGD peptide, PD98059 or FAK and ERK2 mutant. Taken together, our results indicated that OPN enhances the migration of chondrosarcoma cells by increasing MMP-9 expression through the alphavbeta3 integrin, FAK, MEK, ERK and NF-kappaB signal transduction pathway.
Chen
Ying-Ju
YJ
School of Pharmacy, China Medical University, Taichung, Taiwan.
Wei
Ying-Ying
YY
Chen
Hsien-Te
HT
Fong
Yi-Chin
YC
Hsu
Chin-Jung
CJ
Tsai
Chun-Hao
CH
Hsu
Horng-Chaung
HC
Liu
Shing-Hwa
SH
Tang
Chih-Hsin
CH
D045744:Cell Line, Tumor; D002465:Cell Movement; D002813:Chondrosarcoma / Q000201:enzymology* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D053495:Osteopontin / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D039302:Integrin alphaVbeta3; D016328:NF-kappa B; D053495:Osteopontin; D051417:Focal Adhesion Kinase 1; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9