SCANNING ELECTRON-MICROSCOPY OF MULTIDRUG-RESISTANT CELLS IN HEMATOLOGICAL AND MAMMARY MALIGNANCIES

Multidrug resistance (MDR) is frequently found in haematologic maligna ncies. It has been shown that MDR is often related to the expression o f a membrane glycoprotein (P-170) which actively pumps many hydrophobi c agents out of the cells. Previous electron microscopic investigation s revealed morphological differences between P-388 resistant and P-388 sensible cell membranes, but the modulation of the membrane morpholog y seems to be related to the tumor-cell environment. In order to estab lish if morphological differences exist between sensitive and resistan t cells, both sensitive and resistant strains from three different cel l lines were studied by scanning electron microscopy: human leukaemia CEM and vinblastin resistant cells (CEM/VBL100), human breast cancer M CF-7 and mice leukaemia P-388 with the doxorubicin resistant strains ( MCF-7/DX and P-388/DX, respectively). The surface of the membranes of the sensitive cells was regular, unlike the resistant ones which prove d to be irregular, endowed with long villus-like processes or numerous folds and ruffles. The addition of albumin to the culture medium indu ced a shift from the resistant to the sensitive phenotype, thus sugges ting that the P-388/DX morphology may be linked to the concentration o f protein in the culture medium. Exposure to DX, verapamil (VRP) or mo noclonal antibody against P-170 (mAb-57) did not modify the surface of the resistant strains, demonstrating that surface irregularities are probably not linked to P-glycoprotein function. Blasts from four P-170 positive leukaemic patients were also analyzed: an irregular shape wa s always found.