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Journal of Cell Science, Vol 102, Issue 3 447-456, Copyright © 1992 by Company of Biologists
JOURNAL ARTICLES |
I Ellis, AM Grey, AM Schor and SL Schor
Department of Cell and Structural Biology, University of Manchester, UK.
The migration of adult skin fibroblasts into three-dimensional collagen gel matrices is differentially affected by cell density, with subconfluent cells displaying a significantly elevated level of migration compared to confluent ones. Fetal fibroblasts differ from adult cells in that they display an elevated level of migration at both subconfluent and confluent cell densities. We have previously reported that this difference in behaviour results from the secretion by fetal fibroblasts of a 'migration stimulating factor' (MSF) which is not made by their normal adult counterparts, and that MSF appears to act by stimulating the synthesis of hyaluronic acid (HA). Data presented in this communication indicate that (a) MSF specifically stimulates the synthesis of high molecular weight species of HA, (b) TGF-beta 1 inhibits the elevated migration of adult fibroblasts plated at subconfluent cell density, (c) under these conditions, TGF-beta 1 induces a parallel decrease in the synthesis of high molecular weight HA and increase in the synthesis of low molecular weight HA, (d) TGF-beta 1 is a potent antagonist of MSF, effectively blocking its stimulation of cell migration and synthesis of high molecular weight HA, and (e) the inhibition of fibroblast migration by TGF-beta 1 does not appear to be a chemotactic response dependent upon the existence of a concentration gradient of the cytokine. Our observations regarding the inhibitory effects of TGF-beta 1 on fibroblast migration into 3D collagen gels stand in marked contrast to various published reports indicating that this cytokine stimulates the migration of human skin fibroblasts through the pores of polycarbonate filters as used in modified Boyden chamber assays; this discrepancy underscores the importance of the substratum in modulating cellular response to cytokines. Our results are discussed in terms of the possible combined contribution of MSF and TGF-beta 1 to wound healing.
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  R. A. Kay, I. R. Ellis, S. J. Jones, S. Perrier, M. M. Florence, A. M. Schor, and S. L. Schor The Expression of Migration Stimulating Factor, a Potent Oncofetal Cytokine, Is Uniquely Controlled by 3'-Untranslated Region-Dependent Nuclear Sequestration of Its Precursor Messenger RNA Cancer Res., December 1, 2005; 65(23): 10742 - 10749. [Abstract] [Full Text] [PDF]
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S. L. Schor, I. R. Ellis, S. J. Jones, R. Baillie, K. Seneviratne, J. Clausen, K. Motegi, B. Vojtesek, K. Kankova, E. Furrie, et al. Migration-Stimulating Factor: A Genetically Truncated Onco-Fetal Fibronectin Isoform Expressed by Carcinoma and Tumor-Associated Stromal Cells Cancer Res., December 15, 2003; 63(24): 8827 - 8836. [Abstract] [Full Text] [PDF]
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 P. A. Hogg, I. Grierson, and P. Hiscott Direct Comparison of the Migration of Three Cell Types Involved in Epiretinal Membrane Formation Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2749 - 2757. [Abstract] [Full Text] [PDF]
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P. Hogg, M. Calthorpe, M. Batterbury, and I. Grierson Aqueous Humor Stimulates the Migration of Human Trabecular Meshwork Cells In Vitro Invest. Ophthalmol. Vis. Sci., April 1, 2000; 41(5): 1091 - 1098. [Abstract] [Full Text]
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 I Ellis, J Banyard, and S. Schor Differential response of fetal and adult fibroblasts to cytokines: cell migration and hyaluronan synthesis Development, January 4, 1997; 124(8): 1593 - 1600. [Abstract] [PDF]
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 S. Schor, I Ellis, C Dolman, J Banyard, M. Humphries, D. Mosher, A. Grey, A. Mould, J Sottile, and A. Schor Substratum-dependent stimulation of fibroblast migration by the gelatin-binding domain of fibronectin J. Cell Sci., January 10, 1996; 109(10): 2581 - 2590. [Abstract] [PDF]
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C. Irwin, M Picardo, I Ellis, P Sloan, A Grey, M McGurk, and S. Schor Inter- and intra-site heterogeneity in the expression of fetal-like phenotypic characteristics by gingival fibroblasts: potential significance for wound healing J. Cell Sci., January 5, 1994; 107(5): 1333 - 1346. [Abstract] [PDF]
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