Autonomous migration of human fetal skin fibroblasts into a denuded area in a cell monolayer is mediated by basic fibroblast growth factor and collagen.
Human fetal skin fibroblasts (TIG-3S) were found to migrate into a denuded area in a cell monolayer when cultured in both serum-depleted and serum-supplemented media, unlike adult-donor skin fibroblasts which migrated well only when cultured in serum-supplemented medium. Therefore, a series of experiments was carried out to determine whether autocrine factors are involved in their migration. The migration of TIG-3S cells in serum-depleted medium was suppressed by the addition of suramin, a factor with growth factor antagonist properties, which suggests that growth factors are important for cell migration. The suramin-induced inhibition was reversed completely by adding excess basic fibroblast growth factor (bFGF) to the culture medium and partially by platelet-derived growth factor (PDGF). Treatment with neutralizing anti-PDGF antibody did not suppress TIG-3S cell migration, whereas neutralizing anti-bFGF antibody did, which indicates that bFGF is an autocrine and PDGF a paracrine factor involved in cell migration. Next, an experiment was performed to ascertain whether the extracellular matrix is involved in TIG-3S cell migration. Monensin, an inhibitor of extracellular matrix secretion, inhibited cell migration, which was reversed by adding excess type I collagen, but not excess plasma fibronectin. In addition, further evidence for the involvement of collagen was provided by the observation that ethyl-3,4-dihydroxybenzoate, a specific inhibitor of collagen synthesis, suppressed cell migration. These results suggest that the autonomous migration of TIG-3S human fetal skin fibroblasts is mediated by bFGF and type I collagen, which they produce and secrete.
Kondo
H
H
Department of Experimental Biology, Tokyo Metropolitan Institute of Gerontology, Japan.
Matsuda
R
R
Yonezawa
Y
Y
D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D003094:Collagen / Q000494:pharmacology*; D003470:Culture Media; D005109:Extracellular Matrix / Q000502:physiology; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology; D008297:Male; D008985:Monensin / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D013498:Suramin / Q000494:pharmacology
D000975:Antioxidants; D003470:Culture Media; D005353:Fibronectins; D006133:Growth Substances; D062385:Hydroxybenzoates; D016222:Fibroblast Growth Factor 2; C018063:ethyl protocatechuate; D013498:Suramin; D003094:Collagen; D008985:Monensin