Functional role for the 170- to 180-kDa glycoprotein specific to drug-resistant tumor cells as revealed by monoclonal antibodies.

An overexpression of the plasma membrane glycoprotein of relative molecular size 170-180 kDa is consistently found in different multidrug-resistant human and animal cell lines, although the functional role of the protein in multidrug resistance is not known. Two monoclonal antibodies that interfere with biochemical functions were generated against the human myelogenous leukemia K-562 cells resistant to adriamycin (K-562/ADM). These antibodies, designated MRK16 and MRK17, are specifically reactive to K-562/ADM and a human ovarian cancer cell line resistant to adriamycin (2780AD). MRK16 modulated vincristine and actinomycin D transport in the resistant cells, while MRK17 specifically inhibited the growth of the resistant cells. Both antibodies recognized the 170- to 180-kDa glycoprotein. These data indicate that the 170- to 180-kDa glycoprotein is involved, directly or indirectly, in the drug transport mechanisms and the proliferation of multidrug-resistant tumor cell lines.