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.

Highlights

  • CD150 (IPO3/SLAM, for Signaling Lymphocytic Activation Molecule) is a membrane protein that belongs to the SLAM family within the immunoglobulin superfamily of surface receptors

  • To find out whether CD150 is expressed in brain tissues and tumors of the central nervous system we performed immunohistochemical studies of primary human CNS tumors (108 cases) and brain tissues from patients with non-tumor pathology

  • The highest level of CD150 expression was found in glioblastoma, which had the highest incidence of CD150 positive cases (88.9% of cases) (Fig. 1A, Table 1)

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Summary

Introduction

CD150 (IPO3/SLAM, for Signaling Lymphocytic Activation Molecule) is a membrane protein that belongs to the SLAM family within the immunoglobulin superfamily of surface receptors. In addition to the transmembrane form of CD150 (mCD150), cells of hematopoietic lineage express mRNA encoding the secreted form of CD150 (sCD150), which lacks the entire transmembrane region of 30 amino acids [4,10,11]. They express mRNAs of the cytoplasmic form (cCD150) lacking the leader sequence, and a variant membrane CD150 (vmCD150 or tCD150) with a truncated cytoplasmic tail [12]. Expression of the vmCD150 isoform was not confirmed at the mRNA level [11]

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