Altered Surface Membrane Glycoproteins in Vinca Alkaloid-resistant Human Leukemic Lymphoblasts

Abstract

Starting with an established line of human leukemic lymphoblasts (CCRF-CEM), we have developed sublines with varying degrees of resistance to vinblastine by growth in the presence of sublethal concentrations of drug. The resistance of these sublines to vinblastine ranges from 10.6-fold to more than 2000-fold when compared with the sensitive parent cells. These vinblastine-resistant cells tend to form large aggregates in stationary suspension culture, suggesting the possibility of an alteration in the cell surface membrane. The surface glycoproteins of sensitive and vinblastine-resistant CCRF-CEM cells were examined by the galactose oxidase (with or without neuraminidase)-[³H]borohydride procedure. It was found that a glycoprotein with a molecular weight of 170,000 to 190,000 is present on the surface of the drug-resistant cells. This prominent glycoprotein appears to be related to the degree of resistance in that it increases in amount with increased resistance to vinblastine. This relationship obtains with cells up to 269 times more resistant to this drug than is the sensitive parent line. Further increases in the degrees of resistance apparently do not lead to greater amounts of this glycoprotein, suggesting that the changes in the cell surface seen with resistance are not absolute or are not all detectable by the surface-labeling method used in this study. Finally, cells selected for high resistance to 1-β-d-arabinofuranosylcytosine have a cell surface glycoprotein pattern similar to that of the sensitive parent line, indicating that the altered glycoprotein profile shown here is not a characteristic of resistance in general but is rather associated with resistance to such Vinca alkaloids as vinblastine.