Mutually antagonistic effects of hydrocortisone and retinyl acetate on envelope competence in cultured malignant...

Serially propagated SCC-13 keratinocytes, derived from a human squamous cell carcinoma, are greatly influenced by culture conditions in their ability to form ionophore-inducible cross-linked envelopes. Supplementation of the growth medium with fetal bovine serum at concentrations ranging from 0.5 to 20 percent had little effect on competence to form envelopes in confluent cultures. At each serum concentration, however, addition of hydrocortisone to the medium led to an increase in competence of almost fourfold, from approximately 20 to nearly 80 percent. With the serum supplementation held at 5 percent, addition of retinyl acetate to the medium suppressed competence in a concentration-dependent manner over the range of 1 to 100 ng/ml. At the highest concentration employed, competence was reduced over fourfold in the presence of hydrocortisone and virtually eliminated in its absence. When the cells were grown using serum depleted of endogenous vitamin A, a majority were competent in the absence of hydrocortisone. Under this condition, retinyl acetate suppressed competence over fivefold in the absence of hydrocortisone, but not at all in its presence. We conclude that hydrocortisone stimulates envelope competence primarily by antagonizing the suppressive effect of vitamin A. The SCC-13 cell line may prove valuable in studying mechanisms of retinoid and corticosteroid therapeutic action on diseased human keratinocytes.