Calcium regulation of heparan sulfate proteoglycans in breast cancer cells

Breast tumor cells have been shown to be responsive to calcium in that external calcium modifies cell calcium, shape and growth. In order to highlight some of the numerous mechanisms by which calcium is operating, we investigated its influence on the cell microenvironment and particularly its effect on membrane-associated heparan sulfate proteoglycans. The breast cancer cells MCF-7 were grown either at low (0.04 mM) or high (2.5 mM) calcium concentration. After 3 days of culture, cells were labeled with Na₂³⁵SO₄ for 24 h and cell-associated proteoglycans extracted and purified. We showed that calcium enhances approximately twofold the synthesis of sulfated proteoglycans and, among these sulfated proteoglycans, chemical treatments indicated a specific two-to threefold increase of heparan sulfate proteoglycans. In view of the increasing implication of heparan sulfate proteoglycans in numerous mechanisms such as cell-cell contact, cell-matrix interactions and cell growth control, it appears that calcium may be a target for modulating metastatic and growth processes in breast tumor cells.Abbreviations PG proteoglycans - HSPG heparan sulfate proteoglycans - GAG glycosaminoglycansThis work was supported by grants from la Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC), les Comités du Nord et du Pas-de-Calais de la FNCLCC, La Caisse Régionale d'Assurance Maladie and by funds from the University of Lille II. The authors are indebted to Dr B. Lassalle, Centre d'Analyse d'Images, University of Lille I, for cell cycle study