Dexamethasone enhances expression of membrane and soluble interleukin-6 receptors by prostate carcinoma cell lines

Primary prostate carcinoma cells constitutively secrete interleukin-6 (IL-6), and high levels of IL-6 receptor are detected in prostate carcinoma tissues. These findings have implicated IL-6 in the growth and differentiation of prostate carcinomas. Herein, we examined the regulation of IL-6 receptor complex (IL-6R alpha/gpl30) in prostate carcinoma cell lines. We also analyzed the production of soluble IL-6R alpha (IL-6sR) because IL-6sR can confer the IL-6 responsiveness on IL-6R alpha-lacking cells.

Three established prostate carcinoma cell lines, PC-3, DU 145 and LNCaP, were analyzed. Protein tyrosine-phosphorylation was detected by immunoblotting. The expression of IL-6R alpha, gpl30 and IL-6sR was determined by RT-PCR, flow cytometry and ELISA.

IL-6 induced tyrosine-phosphorylated proteins in LNCaP but not in PC-3 or DU 145, indicating that LNCaP cells express the functional IL-6 receptor. Dexamethasone (Dex)-treatment induced functional IL-6 receptors on DU 145 and PC-3 through upregulation of IL-6R alpha and gpl30. In addition, LNCaP, Dex-treated PC-3 and Dex-treated DU 145 secreted large amounts of IL-6sR.

The expression of IL-6 receptor by prostate carcinoma cell lines was augmented by glucocorticoid. We propose prostate carcinomas as IL-6sR producing tumors, and IL-6sR may modulate the behavior of not only the tumor cells but also the surrounding cells.