[Involvement of sulfated proteoglycans in the control of proliferation of MCF-7 breast cancer cells].
The MCF-7 breast cancer cells exhibit remarkable growth enhancement in response to basic fibroblast growth factor (FGF-2) stimulation in a dose dependent manner. To investigate the involvement of proteoglycans on control of FGF-2 induced proliferation, polysaccharide chains were degraded by specific enzymes. Our results showed that MCF-7 cells were unsensitive to FGF-2 after enzymatic degradation of heparin sulfate proteoglycans (HSPG) by heparinase. After metabolic inhibition of sulphation by sodium chloride, radiolabelled proteoglycans were purified and quantified by ion exchange chromatography. Sodium chlorate treatment reduced by 70% sulfation of proteoglycans. This decrease of sulphation totally inhibited FGF-2-mediated proliferation. The sulphated glycosaminoglycans which were critical in FGF-2-induced proliferation were strictly HSPG, as an addition of heparin in cell culture medium can restore FGF-2 mitogenic activity. In contrast, other glycosaminoglycans (chondroitin sulfate/hyaluronic acid) did not show any effect. These results provide clear evidence for the critical role of HSPG in FGF-2-induced proliferation on MCF-7 breast cancer cells.
Delehedde
M
M
Laboratoire de biologie cellulaire et moléculaire du développement, Université des sciences et technologies de Lille, France.
Deudon
E
E
Boilly
B
B
Hondermarck
H
H
D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division; D002704:Chlorates / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism / Q000494:pharmacology; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000494:pharmacology; D006801:Humans; D011509:Proteoglycans / Q000096:biosynthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D002704:Chlorates; D016222:Fibroblast Growth Factor 2; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; C032706:sodium chlorate
Implication des protéoglycanes sulfatés dans le contrôle de la prolifération des cellules cancéreuses mammaires MCF-7.