Calcium-dependent proliferation of NG108-15 neuroblastoma cells

While there is increasing evidence that Ca2+ plays an important role in regulating cell proliferation, the precise mechanisms have not been clearly elucidated so far. In order to gain insight into how Ca2+ controls cell division, the rate of proliferation, cell volume, viability and attachment to the culture support were measured in NG108-15 neuroblastoma cells in the presence of various extracellular Ca2+ concentrations ([Ca2+](o)). Culture medium [Ca2+](o) was decreased from 1.8 mmol/l to various values down to 1 mumol/l with EGTA. The rate of cell proliferation was almost independent of [Ca2+]. between 1.8 mmol/l and 45 mumol/l. It was decreased by about 50% at 12 mumol/l Ca2+ and was almost zero in the presence of 1 mumol/l Ca2+. As we hawe shown previously (Rouzaire-Dubois and Dubois 1998) long term hypertonicity increased the cell volume and decreased the rate of proliferation. The effects of hypertonicity and decrease in [Ca2+](o) on cell proliferation were synergistic and can be described by cell size-dependent and independent mechanisms, respectively. Relative to control conditions (1.8 mmol/l Ca2+), decreases in [Ca2+](o) to 12 and 1 mumol/l decreased the cell viability to 76 and 52% and the cell adhesion to dishes to 16 and 3%, respectively. Altogether, these results indicate that the effects of alteration in [Ca2+](o) and cell size on neuroblastoma cell proliferation are independent and act on different signalling pathways controlling cell division.