title: Syndecan-1 regulates FGF8b responses in S115 mammary carcinoma cells.
abstract: In murine mammary carcinoma cells Shionogi 115 (S115) testosterone induces phenotypical transformation which is largely due to expression of fibroblast growth factor (FGF) 8b. Concomitantly, the expression of the cell surface heparan sulfate proteoglycan syndecan-1 is down-regulated. However, if syndecan-1 expression is maintained by transfection with a testosterone-driven syndecan-1 construct, transformation does not occur. Here we have investigated how the down-regulation of syndecan-1 expression in testosterone-treated S115 cells and the high level of expression in syndecan-1 transfected cells influence the cellular responses toward FGF8b. Our results show that high level of syndecan-1 is associated with a decreased magnitude and duration of the FGF8b induced Erk phosphorylation. This effect was observed regardless whether the cells were stimulated directly with exogenous FGF8b or with testosterone to induce autocrine FGF8b production. Moreover, syndecan-1 transfected cells did not respond to FGF8b stimulation by increase in the intracellular free calcium, whereas untransfected cells displayed a rapid (10 s) induction. These data suggest that, in S115 cells, syndecan-1 acts as a modulator of FGF8b signaling that can limit cellular responses to FGF receptor activation. The decreased levels of syndecan-1 expression and upregulation of the FGF signaling system seen in many cancers may contribute to the proliferation of the malignant cells in vivo.
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Finland.
authors.forename: Leif
authors.initials: L
authors.lastname: Viklund
authors.forename: Natalia
authors.initials: N
authors.lastname: Vorontsova
authors.forename: Tiina
authors.initials: T
authors.lastname: Henttinen
authors.forename: Markku
authors.initials: M
authors.lastname: Salmivirta
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism*; D015870:Gene Expression; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D011509:Proteoglycans / Q000502:physiology*; D053668:Syndecan-1; D053667:Syndecans; D013739:Testosterone / Q000502:physiology; D014170:Transformation, Genetic
chemical_list: D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D051524:Fibroblast Growth Factor 8; D013739:Testosterone; D048049:Extracellular Signal-Regulated MAP Kinases