Modification of membrane parameters (antigen expression and electrophysiological characteristics) and cell differentiation

Cholesterol and phospholipids play an important role in the modulation of plasma membrane fluidity which in turn affects cell behaviour. Several transformed cells display an increased membrane fluidity; in fact, some reports have indicated that metastatizing cells possess a more fluid plasma membrane than the original tumor cells. By growing tumor cells in the presence of cholesterol, differentiation process might, in some respect, be influenced. HT 29 cells, an established cell line of human colon adenocarcinoma, were grown in RPMI 1640 medium containing cholesterol at 25, 50 and 100 µg/ml concentrations. Only in the case of the highest cholesterol concentration the number of cells at confluence was reduced; in addition, cholesterol stimulated carcinoembrionic antigen expression. Electrical membrane potential measured with microelectrodes was -19.6 ± 0.9 mV (n = 28) in controls and -23.6 ± 1.6 mV (n = 25) in the presence of cholesterol. The lowering of the external K+ concentration below that present in the medium resulted in a hyperpolarization that was higher in the presence than in absence of cholesterol. On the contrary, the increase of the external K+ concentration led to a depolarization greater in controls than in the presence of cholesterol. It would, therefore, seem that cholesterol increases the electrical resistance of the plasma membrane of HT 29 cells. Finally, cholesterol-treated cells showed at the electron microscope the disappearance of intracytoplasmic lumina and the tendency of microvilli to settle at one pole of the cell; both phenomena seem to indicate an attempt of the cell to differentiate.