Glucocorticoid-induced alterations of morphology and growth of fibrosarcoma cells derived from 7,12-dimethylbenz(a)anthracene rat mammary tumor.

Cloned cell strains with adverse patterns of differentiation obtained from 7,12-dimethylbenz(a)anthracene-induced rat mammary tumor tissue were used to study the effects of glucocorticoid hormones on morphology and proliferation. HH-16 clone 2/1 cells apparently reflecting mesenchymal cells of the stromal part of the mammary gland grow as elongated, mostly bipolar fibroblasts in criss-cross patterns. When cultured in the presence of glucocorticoids, the cells flattened, lost bipolarity, extended in size, and showed arrest of growth at confluence, possibly due to contact inhibition. Immunocytochemical examination of dexamethasone-treated cells revealed actin cables which were absent in untreated cells. The hormone-treated cells expressed Mr 50,000-67,000 cytokeratins, and the extracellular matrix proteins fibronectin and laminin were increased. The in vitro effects on morphology and growth were reversible 3-4 days after withdrawal of the glucocorticoids. In dexamethasone-treated animals the growth of fibrosarcomas produced by inoculation of newborn rats with HH-16 clone 2/1 cells was reduced, and the survival time of the tumor-bearing animals was extended. Apparently, morphology and growth of HH-16 clone 2/1 fibrosarcoma cells can be controlled by glucocorticoids. In comparison, epithelioid HH-16 clone 4 cells established simultaneously from 7,12-dimethylbenz(a)anthracene-induced rat mammary tumor were unresponsive to glucocorticoids.