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

Anticancer Res. 1998 Nov-Dec;18(6A):4403-8.

Abstract

Background: 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.

Material and methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / immunology
  • Culture Media, Conditioned
  • Dexamethasone / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Male
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Prostatic Neoplasms / immunology*
  • RNA, Messenger / genetics
  • Receptors, Interleukin-6 / analysis
  • Receptors, Interleukin-6 / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured
  • U937 Cells

Substances

  • Culture Media, Conditioned
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, Interleukin-6
  • Phosphotyrosine
  • Dexamethasone