Stimulation of gelatinase B and tissue inhibitors of metalloproteinase (TIMP) production in co-culture of human osteosarcoma cells and human fibroblasts: gelatinase B production was stimulated via up-regulation of fibroblast growth factor (FGF) receptor.
Co-cultures of human osteosarcoma Takase (OST) cells with various human fibroblasts derived from surgical specimens stimulated production of gelatinase B (92-kDa type-IV collagenase, MMP-9), tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-2 when compared to cultures of individual cells. The maximum stimulation of gelatinase-B production occurred at a cellular ratio of 1:1. Conditioned media from several fibroblast cultures stimulated OST cells to produce gelatinase B, TIMP-1 and TIMP-2, but not vice versa. Among various recombinant growth factors or cytokines, tumor necrosis factor (TNF)-alpha stimulated gelatinase-B production in cultures of OST cells alone, while recombinant basic fibroblast growth factor (bFGF) stimulated gelatinase-B production in co-cultures of OST cells with skin fibroblasts but not in individual cultures of each cell type. In the co-cultures, gelatinase-B production was inhibited by anti-bFGF monoclonal antibody (MAb), but not by anti TNF-alpha MAb. This co-culture-specific stimulation of gelatinase-B production by bFGF was associated with increased expression of the FGF receptor in the co-culture.
Kurogi
T
T
Department of Pathology, Miyazaki Medical College, Kiyotake, Miyazaki, Japan.
Nabeshima
K
K
Kataoka
H
H
Okada
Y
Y
Koono
M
M
D000818:Animals; D002478:Cells, Cultured; D017364:Collagenases / Q000378:metabolism*; D003470:Culture Media; D016207:Cytokines / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology*; D006023:Glycoproteins / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9; D051379:Mice; D012516:Osteosarcoma / Q000201:enzymology*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases; D015854:Up-Regulation
D003470:Culture Media; D016207:Cytokines; D006023:Glycoproteins; D006133:Growth Substances; D017468:Receptors, Fibroblast Growth Factor; D019714:Tissue Inhibitor of Metalloproteinases; D016222:Fibroblast Growth Factor 2; D017364:Collagenases; D020780:Matrix Metalloproteinase 9