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Immunological delineation in normal and malignant cells of a membrane protein involved in glucose transport. II. Function of the antigen.

A review of the literature suggested that the antigen detected by the M/27 antibody described in the preceding paper might be involved in the transport of glucose across the cell membrane. This idea was tested by measuring the amount of M/27 antibody bound to cells under a range of conditions known to influence the rate of glucose uptake. Glucose starvation and the administration of insulin under appropriate conditions are known to increase the Vmax for glucose uptake in certain cells, and high cell density in vitro is known to decrease the Vmax. Glucose starvation was found to increase the amount of M/27 antigen present on the surface of 2 malignant cell lines, but produced no detectable change in 5 different non-malignant cell types. Insulin increased the amount of M/27 antigen on the surface of both malignant and non-malignant cells. At high cell density, the amount of M/27 antigen present on the cell surface decreased. The changes in the Vmax for glucose uptake produced by these manipulations have been shown not to require the synthesis of protein. This was also found to be true for the changes in M/27 antigen concentration. By disrupting cells in detergent, it could be shown that there was an intracellular pool of M/27 antigen. The total amount of M/27 antigen in the cell was found to be about 4 times as large as the amount of the antigen on the cell surface. This figure agrees with the value given in the literature for the size of the intracellular pool of the glucose transport system. The amount of M/27 antigen on the cell surface was found to vary during the cell cycle. A dramatic increase occurred early in S phase.