Expression of soluble interleukin-6 receptor in malignant ovarian tissue

Am J Obstet Gynecol. 2010 Sep;203(3):230.e1-8. doi: 10.1016/j.ajog.2010.03.034. Epub 2010 May 14.

Abstract

Objective: The objective of the study was to investigate interleukin-6 receptor (IL6R) isoforms and sheddases in the ovarian tumor microenvironment.

Study design: Expression of IL6R and sheddases was measured in tissue samples of papillary serous ovarian carcinomas and benign ovaries by real-time polymerase chain reaction and immunohistochemistry. Murine xenograft samples were tested by enzyme-linked immunosorbent assay to discriminate and evaluate tumor and host contributions of IL6R.

Results: IL6R expression was increased in malignant ovarian tumors and localized to epithelial cells. Expression of a soluble splice variant of IL6R was increased in malignant tumors, as were the sheddases for the full-length isoform. An in vivo xenograft model showed that host IL6R expression is also increased and regulated by tumor-associated inflammation.

Conclusion: IL6R is overexpressed in epithelial ovarian malignancies because of increases in a soluble IL6R variant, in the sheddases for full-length IL6R and host IL6R expression. Soluble IL6R may be an efficacious target for reducing IL6-mediated ovarian tumor progression.

Publication types

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

MeSH terms

  • ADAM Proteins / metabolism
  • ADAM10 Protein
  • ADAM17 Protein
  • Adenocarcinoma, Clear Cell / metabolism
  • Adult
  • Aged
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Cell Line, Tumor
  • Cystadenocarcinoma, Papillary / metabolism
  • Cystadenocarcinoma, Serous / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukin-6 / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Middle Aged
  • Ovarian Neoplasms / metabolism*
  • Ovary / metabolism
  • Polymerase Chain Reaction
  • Protein Isoforms
  • RNA / metabolism
  • Receptors, Interleukin-6 / metabolism*
  • Up-Regulation

Substances

  • Interleukin-6
  • Membrane Proteins
  • Protein Isoforms
  • Receptors, Interleukin-6
  • RNA
  • Amyloid Precursor Protein Secretases
  • ADAM Proteins
  • ADAM10 Protein
  • ADAM10 protein, human
  • ADAM17 Protein