Expression of short-form oncostatin M receptor as a decoy receptor in lung adenocarcinomas

J Pathol. 2008 Jul;215(3):290-9. doi: 10.1002/path.2361.

Abstract

Oncostatin M (OSM) is a member of the interleukin-6 (IL-6) family of cytokines, and binds to the OSM receptor (OSMR) to inhibit cancer growth. Four forms of OSMR have been identified: leukemia inhibitory factor receptor (LIFR), OSMR beta, short-form OSMR (OSMRs) and soluble OSMR (sOSMR). In this study, we examined the type and expression of OSMR in lung adenocarcinomas (LADCs). Expression of OSMR was determined by reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting, immunohistochemistry and confocal immunofluorescent microscopy (CIM). Our results showed that, among the four forms of OSMR, OSMRs was mainly expressed in LADC, and expression level of OSMRs correlated with patient survival. CIM revealed that OSMRs was localized on the cell membrane of LADC cell lines in vitro. OSMRs acts as a decoy receptor by reducing the inhibitory effect of OSM on cell growth. Decrease in OSMRs expression by siRNA increased cell sensitivity to OSM, and ectopic expression of OSMRs reduced cell sensitivity to OSM. These results suggest that expression of OSMRs, which operates as a decoy receptor for OSM, is correlated with disease progression and adverse prognosis in patients with LADC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / chemistry*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Cell Membrane / chemistry
  • Cell Membrane / ultrastructure
  • Chi-Square Distribution
  • Female
  • Gene Expression
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Lung Neoplasms / chemistry*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Microscopy, Confocal
  • Oncostatin M / analysis
  • Oncostatin M / genetics
  • Oncostatin M / metabolism
  • Oncostatin M Receptor beta Subunit / analysis
  • Oncostatin M Receptor beta Subunit / genetics
  • Oncostatin M Receptor beta Subunit / metabolism
  • Prognosis
  • RNA Interference
  • RNA, Small Interfering / pharmacology
  • Receptors, OSM-LIF / analysis
  • Receptors, OSM-LIF / genetics
  • Receptors, Oncostatin M / analysis*
  • Receptors, Oncostatin M / genetics
  • Receptors, Oncostatin M / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate

Substances

  • Oncostatin M Receptor beta Subunit
  • RNA, Small Interfering
  • Receptors, OSM-LIF
  • Receptors, Oncostatin M
  • Oncostatin M