Calcitonin-induced NF-κB activation up-regulates fibronectin expression in MG63 osteosarcoma cells.
Salmon calcitonin has been used extensively as a therapeutic tool in the regulation of bone remodeling. However, there is a growing body of evidence indicating that the calcitonin peptides are involved in regulation of cell growth, differentiation, survival and tissue development. In the present study, we investigated the effect of calcitonin in cell matrix interactions in MG63 cell line. Our results demonstrated that calcitonin increases cell growth of MG63 osteosarcoma cells in parallel with serine/threonine protein kinase B (AKT/PKB) activation. Moreover, calcitonin induced up-regulation of fibronectin expression in a nuclear factor-kappa B (NF-κB)-dependent manner, accompanied by enhanced enzymatic activity of matrix metalloproteinase-9 (MMP-9) and increased expression of tissue inhibitors of MMP-1 and -2. MMP-9 stimulation with calcitonin was accompanied by an increase in protein expression of the α5β1 integrin receptor. To our knowledge, our results demonstrate, for the first time, that calcitonin is a potent inducer of fibronectin, an extacellular matrix component that is suggested to have a pro-oncogenic and healing effect, in a NF-κB-dependent manner.
Institute of Biology, National Center for Scientific Research Demokritos, Ag. Paraskevi, Athens, Greece. atzin@bio.demokritos.gr.
Ioanna
I
Tsagaraki
Constantinos
C
Phenekos
Effie
E
Tsilibary
Athina
A
Tzinia
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002116:Calcitonin / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D050071:Bone Density Conservation Agents; D005353:Fibronectins; D016023:Integrins; D016328:NF-kappa B; D002116:Calcitonin; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
Calcitonin; MG63 cells; NF-κB activation; fibronectin; integrins; matrix metallo-proteinase 9