Expression of CD150 in tumors of the central nervous system: identification of a novel isoform

PLoS One. 2015 Feb 24;10(2):e0118302. doi: 10.1371/journal.pone.0118302. eCollection 2015.

Abstract

CD150 (IPO3/SLAM) belongs to the SLAM family of receptors and serves as a major entry receptor for measles virus. CD150 is expressed on normal and malignant cells of the immune system. However, little is known about its expression outside the hematopoietic system, especially tumors of the central nervous system (CNS). Although CD150 was not found in different regions of normal brain tissues, our immunohistochemical study revealed its expression in 77.6% of human CNS tumors, including glioblastoma, anaplastic astrocytoma, diffuse astrocytoma, ependymoma, and others. CD150 was detected in the cytoplasm, but not on the cell surface of glioma cell lines, and it was colocalized with the endoplasmic reticulum and Golgi complex markers. In addition to the full length mRNA of the mCD150 splice isoform, in glioma cells we found a highly expressed novel CD150 transcript (nCD150), containing an 83 bp insert. The insert is derived from a previously unrecognized exon designated Cyt-new, which is located 510 bp downstream of the transmembrane region exon, and is a specific feature of primate SLAMF1. Both mCD150 and nCD150 cDNA variants did not contain any mutations and had the leader sequence. The nCD150 transcript was also detected in normal and malignant B lymphocytes, primary T cells, dendritic cells and macrophages; however, in glioma cells nCD150 was found to be the predominant CD150 isoform. Similarly to mCD150, cell surface expression of nCD150 allows wild type measles virus entry to the cell. Our data indicate that CD150 expression in CNS tumors can be considered a new diagnostic marker and potential target for novel therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / chemistry
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • B-Lymphocytes / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Cell Line, Tumor
  • Central Nervous System Neoplasms / metabolism
  • Central Nervous System Neoplasms / pathology
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Regulation*
  • Golgi Apparatus / metabolism
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Measles virus / physiology
  • Molecular Sequence Data
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Splicing
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Signaling Lymphocytic Activation Molecule Family Member 1

Substances

  • Antigens, CD
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Cell Surface
  • SLAMF1 protein, human
  • Signaling Lymphocytic Activation Molecule Family Member 1

Associated data

  • GENBANK/KF471075

Grants and funding

The work was supported by the grant no. 0113U001436 of the National Academy of Sciences of Ukraine (SPS), INSERM (BH), Ligue contre le Cancer (BH), Ministère des affaires Etrangéres (BH), Partenariat Curien Franco-Ukrainien «Dnipro» (SPS, BH), FEBS Summer and Collaborative Fellowships (ORK), Bourse de Gouvernement Français and “AccueilDoc” from Region Rhone Alpes (ORK), Collaborative program of the NAS of Ukraine and the Siberian Department of RAS (SPS, AVT) and the Grant 6.23 from the RAS program Molecular and Cellular Biology (AVT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.