Characterization of the role of IL-6 in the progression of prostate cancer

Prostate. 1999 Feb 15;38(3):199-207. doi: 10.1002/(sici)1097-0045(19990215)38:3<199::aid-pros4>;2-h.


Background: We recently identified IL-6, a pleiotropic cytokine implicated in the neoplastic process of a variety of neoplasms, as a mediator of prostate cancer morbidity. In the present study, we investigated the expression of members of the IL-6 supergene family and related cytokines and the potential role of IL-6 in prostate cancer growth regulation.

Methods: Five established human prostate cancer cell lines were screened by ELISA for production of granulocyte colony-stimulating factor (G-CSF), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), tumor necrosis factor (TNF), interleukin-1 (IL-1), and granulocyte macrophage colony-stimulating factor (GM-CSF). Expression of the ligand-binding component of the IL-6 receptor, IL-6Rp80, was evaluated by ELISA and RT-PCR. Sequential immunoprecipitation and immunoblotting were performed to assay for expression of the signal-transducing component of the IL-6 receptor, gp130. The effects of IL-6 on cell growth were assessed by MTT assays.

Results: The three hormone-refractory cell lines, DU-145, TSU, and PC-3, secreted distinct combinations of cytokines (DU-145: IL-6, GM-CSF; TSU: IL-6, LIF; PC-3: IL-6, G-CSF, LIF, IL-1, GM-CSF), each uniformly expressing IL-6. In contrast, neither of the two hormone-dependent cell lines, LNCaP-ATCC and LNCaP-GW, secreted significant quantities of any of the cytokines analyzed. None of the cell lines secreted detectable quantities of OSM, CNTF, or TNF. All cell lines, irrespective of hormone status, expressed both Il-6Rp80 and gp130. Addition of IL-6 in vitro inhibited growth of hormone-dependent cells, but had no effect on hormone-refractory lines. Anti-IL-6 neutralizing antibody inhibited growth of hormone-refractory cells.

Conclusions: IL-6 appears to undergo a functional transition from paracrine growth inhibitor to autocrine growth stimulator during progression of prostate cancer to the hormone-refractory phenotype.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division / physiology
  • Ciliary Neurotrophic Factor
  • Disease Progression
  • Granulocyte Colony-Stimulating Factor / analysis
  • Growth Inhibitors / analysis
  • Humans
  • Interleukin-1 / analysis
  • Interleukin-6 / genetics
  • Interleukin-6 / physiology*
  • Leukemia Inhibitory Factor
  • Lymphokines / analysis
  • Male
  • Multigene Family*
  • Nerve Tissue Proteins / analysis
  • Oncostatin M
  • Peptides / analysis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / physiopathology*
  • Receptors, Interleukin-6 / analysis
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / analysis


  • Ciliary Neurotrophic Factor
  • Growth Inhibitors
  • Interleukin-1
  • Interleukin-6
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Lymphokines
  • Nerve Tissue Proteins
  • OSM protein, human
  • Peptides
  • Receptors, Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Oncostatin M
  • Granulocyte Colony-Stimulating Factor