MODULATION OF THE IMMUNOPHENOTYPE OF OVARIAN-CANCER CELLS BY N,N-DIMETHYLFORMAMIDE AND TRANSFORMING GROWTH-FACTOR-BETA-1

Exposure of HOC-7 ovarian adenocarcinoma cells to regulators of cell d ifferentiation caused inducer-dependent alterations of the antigenic p attern of the cells. Immunocytochemistry revealed that N, N-dimethylfo rmamide (DMF) elevated the membrane staining for epidermal growth fact or (EGF)-receptor and for desmoplakins I and II. DMF also stimulated c ytoplasmic and surface labeling for CA 125 and the deposition of fibro nectin into the extracellular matrix. Stimulation of fibronectin was a lso seen after addition of transforming growth factor (TGF)-beta1. The se responses were quantified using a fixed-cell, enzyme-linked immunos orbent assay (ELISA) and revealed that DMF dose-dependently induced ex pression of EGF-receptor, CA 125, fibronectin, and desmoplakins I and II. TGF-beta1 stimulated fibronectin and desmoplakins I and II only. P roduction of EGF and TGF-alpha was not affected by these inducers. Imm unocytochemistry, ELISA and Western blotting showed that both inducers caused down-regulation of myc oncoproteins. DMF was more effective in changing the immunophenotype of HOC-7 cells than TGF-beta1. Desmoplak ins I and II demonstrated elevated epithelial differentiation, whereas fibronectin indicated stimulation of extracellular matrix formation. Elevated EGF-receptor could not compensate for the growth inhibition i nduced by DMF. The expression of myc oncoproteins was inversely relate d to cell proliferation. CA 125, however, seems to be unrelated to cel l growth. (C) 1993 Wiley-Liss, Inc.