The stimulation of fibroblasts' collagen synthesis by neoplastic cells is modulated by the extracellular matrix.
Human fibroblasts cocultured with neoplastic MCF7 cells produce increased amounts of collagen. A maximal stimulation requires direct cell-cell contacts between tumor cells and fibroblasts. However, this effect could be reproduced, although to a lesser extent, by medium conditioned by MCF7 cells, suggesting that it is mediated by a factor produced by MCF7 cells and secreted, at least partly, under a soluble form (Noël et al., 1992). This Collagen Stimulating Factor ("COSF") present in the culture medium displayed a molecular mass between 3,500 to 10,000 daltons, bound to heparin and appeared to be different from the growth factors described until now. The "COSF" can be released from the surface of MCF7 cells by treatment with heparin. The aim of the present work was to investigate the influence of various extracellular matrix components on the production and the release of "COSF". A 3- to 4-fold enhancement of collagen synthesis was observed in coculture on plastic and collagen type I substrates without significant modification of the non-collagen proteins. The increased collagen synthesis was paralleled by an elevation of specific collagen mRNAs level suggesting a regulation at a pretranslational level. On the opposite, in the presence of soluble or insoluble laminin, this stimulation was abolished. Similarly, coculture on "reconstituted basement membrane matrix", matrigel, did not increase collagen production. The "COSF" was found to bind to matrigel and could be released from the basement membrane matrix by treatment with heparin.
Noel
A
A
Laboratory of Biology, University of Liege, Belgium.
Munaut
C
C
Nusgens
B
B
Foidart
J M
JM
Lapiere
C M
CM
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003470:Culture Media / Q000494:pharmacology; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007797:Laminin; D008970:Molecular Weight; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D010969:Plastics; D011509:Proteoglycans; D012333:RNA, Messenger / Q000096:biosynthesis; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D003470:Culture Media; D004338:Drug Combinations; D007797:Laminin; D010969:Plastics; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D006493:Heparin; D003094:Collagen