Glucocorticoid hormone renders rat glioma cells dependent on high concentrations of external Ca2+ for growth

C6 rat glioma cells, like other tumor cells, grow optimally in Ca2+-or Mg2+-depleted 5% serum medium. However, the glucocorticoid hormone hydrocortisone renders these cells dependent on high concentrations of external Ca2+ for growth. Upon Ca2+ deprivation (30-80 microM Ca2+ medium) hydrocortisone-treated C6 cells undergo reversible cell-cycle arrest at G0/G1 phase. This effect is specific for glucocorticoid hormones and occurs at physiological concentrations. Growth restimulation of Ca2+-deprived, hydrocortisone-treated C6 cells by bovine pituitary growth factors or serum growth factors only takes place if the external Ca2+ concentration is increased. On the other hand, C6 cell growth requirement for external Mg2+ was not increased by the glucocorticoid hormone treatment. A minimum of 80 microM of external Mg2+ is required to keep cells adhered and spread in Ca2+-depleted (30 microM) 5% serum medium; in high Ca2+ concentration (1.8 mM), Mg2+ is not required for adhesion or spreading. Thus, the hormone hydrocortisone renders the cell cycle of C6 glioma cells controllable by the levels of external Ca2+, a minimal external Mg2+ being necessary to warrant normal adhesion.