Induction of the terminal differentiation of a human squamous cell carcinoma by steroids with glucocorticoid activity.
SqCC/Y1, a human malignant squamous cell carcinoma, spontaneously differentiates when grown to confluence in delipidized serum-containing medium, as measured by the capacity to form detergent-insoluble cornified cell envelopes. Thus, 30% of SqCC/Y1 cells spontaneously attained the differentiated state after 6 days in culture. Exposure of SqCC/Y1 cells to 30, 100, or 300 nM hydrocortisone increased the number of mature cells, producing a 25, 100, and 225%, respective, increase in the number of differentiated cells over the spontaneous rate of maturation. Retinoic acid at levels of 3-300 nM was inhibitory, causing a 24-85% decrease in the number of differentiated cells. Simultaneous treatment with hydrocortisone and retinoic acid indicated mutual antagonism of the effects of these agents on the formation of cornified envelopes. Since hydrocortisone possesses antiangiogenic (AG), mineralocorticoid (MC) and glucocorticoid (GC) activities, steroids with different degrees of GC, MC, and AG potency were examined for their capacities to induce terminal differentiation. Only steroids with GC activity, such as dexamethasone, hydrocortisone, and RU-28362, were capable of increasing the degree of SqCC/Y1 differentiation and antagonizing the inhibitory effects of retinoic acid on the maturation process. In addition, the GC antagonist, RU-38486, reversed the stimulation of cellular differentiation produced by the glucocorticoids. The findings indicate that GC activity is required for the steroid-induced terminal differentiation of SqCC/Y1 cells.
Violette
S M
SM
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
King
I
I
Sartorelli
A C
AC
D019326:17-alpha-Hydroxyprogesterone; D000732:Androstanols / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects*; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D006908:Hydroxyprogesterones / Q000494:pharmacology; D066298:In Vitro Techniques; D015735:Mifepristone / Q000494:pharmacology; D008901:Mineralocorticoids / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D011374:Progesterone / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000732:Androstanols; D005938:Glucocorticoids; D006908:Hydroxyprogesterones; D008901:Mineralocorticoids; D015735:Mifepristone; D003900:Desoxycorticosterone; D011374:Progesterone; D014212:Tretinoin; D019326:17-alpha-Hydroxyprogesterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D006854:Hydrocortisone