Atypical nuclear localization of VIP receptors in glioma cell lines and patients

Biochem Biophys Res Commun. 2014 Nov 28;454(4):524-30. doi: 10.1016/j.bbrc.2014.10.113. Epub 2014 Oct 30.

Abstract

An increasing number of G protein-coupled receptors, like receptors for vasoactive intestinal peptide (VIP), are found in cell nucleus. As VIP receptors are involved in the regulation of glioma cell proliferation and migration, we investigated the expression and the nuclear localization of the VIP receptors VPAC1 and VPAC2 in this cancer. First, by applying Western blot and immunofluorescence detection in three human glioblastoma (GBM) cell lines, we observed a strong nuclear staining for the VPAC1 receptor and a weak nuclear VPAC2 receptor staining. Second, immunohistochemical staining of VPAC1 and VPAC2 on tissue microarrays (TMA) showed that the two receptors were expressed in normal brain and glioma tissues. Expression in the non-nuclear compartment of the two receptors significantly increased with the grade of the tumors. Analysis of nuclear staining revealed a significant increase of VPAC1 staining with glioma grade, with up to 50% of GBM displaying strong VPAC1 nuclear staining, whereas nuclear VPAC2 staining remained marginal. The increase in VPAC receptor expression with glioma grades and the enhanced nuclear localization of the VPAC1 receptors in GBM might be of importance for glioma progression.

Keywords: GPCR; Glioblastoma; Glioma; Nuclear localization; Tissue microarrays; VIP receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Adolescent
  • Adult
  • Aged
  • Cell Nucleus / metabolism*
  • Child
  • Female
  • Glioma / pathology*
  • Humans
  • Male
  • Middle Aged
  • Receptors, Vasoactive Intestinal Peptide, Type II / analysis*
  • Receptors, Vasoactive Intestinal Peptide, Type II / metabolism
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / analysis*
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / metabolism
  • Tissue Array Analysis
  • Tumor Cells, Cultured
  • Young Adult

Substances

  • Receptors, Vasoactive Intestinal Peptide, Type II
  • Receptors, Vasoactive Intestinal Polypeptide, Type I