Tumor-Host Interactions Regulate Glucocorticoid-Mediated Epiglycanin Expression in TA3Ha Murine Mammary Carcinoma Cells

Abstract

The mucin-type glycoprotein epiglycanin is highly expressed on the cell surface of TA3Ha mouse mammary carcinoma cells if the cells are maintained by serial intraperitoneal passage in mice. We found that upon transfer of the cells to growth in vitro in medium supplemented with fetal bovine serum, the expression level of epiglycanin slowly diminished to less than 15% of that in vivo. Repassage of the cells in vivo fully restored the expression of epiglycanin. When TA3Ha cells were cultured in media supplemented with ascites fluid obtained from mice bearing these cells, the high expression level of epiglycanin was maintained. Ascites fluid-containing medium also restored the high expression level of epiglycanin in cells cultured for prolonged periods in vitro. Human ascites fluids obtained from patients with mammary and ovary carcinoma were likewise able to induce the expression of epiglycanin, in contrast to ascites fluids obtained from noncarcinoma patients or serum of healthy individuals. The factor responsible for the upregulation of epiglycanin is heat stable and can be removed from ascites fluids by activated charcoal, suggesting that it is a steroid. Indeed, dexamethasone, at a concentration of 10^–7 mol/l, induced maximal epiglycanin expression within 4 days, and upregulation was inhibited by the glucocorticoid receptor antagonist RU486. However, the maximal induction of epiglycanin expression achieved with ascites fluid was higher, while the kinetics of the induction was much slower, but still RU486 sensitive, than upon treatment with dexamethasone. These results suggest that stimulation of epiglycanin expression by ascites also involves a glucocorticoid. However, the induction in vivo is indirect and involves a cascade of events induced by tumor-host interactions that lead to glucocorticoid-mediated induction of epiglycanin.