Expression of CD150 in Tumors of the Central Nervous System: Identification of a Novel Isoform

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.

SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

“…Our knowledge about CD150 expression and functions outside hematopoietic system is very limited. Protein and mRNA CD150 expression was found in > 70% tumors of CNS, including glioblastoma, astrocytoma, ependymoma and others [33]. Earlier immuhistochemical studies revealed CD150 in squamous cell carcinomas of uterine cervix, esophagus, rectum and oral cavity [26].…”

“…First exon encodes leader peptide of CD150 protein, second -N-terminal variable (V) Ig-like domain, third -N-terminal constant (C2) domain, fourthtransmembrane domain and recently identified new exon (Cyt-new) followed by Cyt1-3 exons encode cytoplasmic part of CD150 ( Fig. 2A) [32,33]. As a result of alternative splicing several structurally different CD150 isoforms are generated: canonical transmembrane CD150 isoform with two immunoreceptor tyrosine-based switch motifs (ITSM) in cytoplasmic tail (mCD150), secreted isoform without transmembrane region (sCD150), novel CD150 isoform (nCD150) with alternative cytoplasmic tail, variable membrane CD150 (vmCD150) isoform, which have truncated cytoplasmic tail, and cytoplasmic CD150 (cCD150) isoform lacking leader sequence (Fig.…”

“…As a result of alternative splicing several structurally different CD150 isoforms are generated: canonical transmembrane CD150 isoform with two immunoreceptor tyrosine-based switch motifs (ITSM) in cytoplasmic tail (mCD150), secreted isoform without transmembrane region (sCD150), novel CD150 isoform (nCD150) with alternative cytoplasmic tail, variable membrane CD150 (vmCD150) isoform, which have truncated cytoplasmic tail, and cytoplasmic CD150 (cCD150) isoform lacking leader sequence (Fig. 2B) [4,33].…”

“…Recently a novel CD150 isoform (nCD150) was found in tumors of central nervous system (CNS). Transcription from Cyt-new exon leads to shift in reading frame and formation of nCD150 isoform with 94 aa cytoplasmic tail lacking classical ITSMs or any another known signaling motifs [33].Besides tumors of CNS nCD150 expression at mRNA level was detected in subpopulation of human tonsillar B cells, normal T cells (CD3 + ), primary DCs, macrophages from peripheral blood, B-lymphoblastoid cell lines, Burkitt's lymphoma cell lines, pre-B acute lymphoblastic leukemia cell lines, HL cell lines, cells of human acute monocytic leukemia cell line THP-1 and MM, primary cases of CLL. It should be noted that nCD150 isoform is predominant in CNS tumors in contrast to normal and malignant B cells where mCD150 is prevailed [31,33,39].…”

The interplay of CD150 and CD180 receptor pathways contribute to the pathobiology of chronic lymphocytic leukemia B cells by selective inhibition of Akt and MAPK signaling

“…Thus, CD150 cell surface expression is a potential surrogate prognostic marker of CLL favourable outcome. Several alternatively spliced isoforms have been reported for CD150: the canonical transmembrane CD150 isoform (mCD150) with two ITSM signaling motifs in the cytoplasmic domain, a secreted CD150 isoform (sCD150) without a transmembrane region, and a novel CD150 isoform (nCD150) with an alternative cytoplasmic tail [ 19 , 20 ]. However, the profile of CD150 isoform expression in CLL has not been analysed.…”