The expression of the MSC-marker CD73 and of NF2/Merlin are correlated in meningiomas

Elmar Kirches, Tabea Steffen, Natalie Waldt, Eva Hebert, Doreen Pachow, Annette Wilisch-Neumann, Gerburg Keilhoff, Thomas Schneider, Werner E K Braunsdorf, Jan-Peter Warnke, Christian Mawrin
Journal of Neuro-oncology 2018, 138 (2): 251-259
Mesenchymal stem cells (MSC) have been found in various cancers and were discussed to influence tumor biology. Cells fulfilling the complete MSC criteria, including surface marker expression (CD73, CD90, CD105) and tri-lineage differentiation, have been isolated solely from a low percentage of high-grade meningiomas. In contrast, pure co-expression of the surface-markers was relatively frequent, raising the question for an additional role of these membrane proteins in meningiomas. Therefore, here we analyzed the expression of CD73, CD90 and CD105 in a series of meningiomas of all grades. Although no significant association of any marker with meningeal tumor growth per se or with tumor-grade was observed, we detected a positive Pearson correlation (r = 0.55, p ≤ 0.05) in low-grade tumors between CD73 and the most relevant tumor suppressor NF2/Merlin, supported by a tendency of lower CD73 expression in cases with allelic losses at the NF2-locus, which express significantly lower NF2/Merlin-mRNA (p ≤ 0.05). In two pairs of syngenous meningeal or meningioma cell lines with or without shRNA-mediated knockdown of NF2/Merlin a nearly complete loss of CD73 mRNA expression was observed after the knockdown (p ≤ 0.001). This suggested that the correlation observed in tumors may result from a direct functional link between Merlin and CD73. Since CD73 is a 5'-exonucleotidase (termed NT5E), we discuss a potential role of NT5E-mediated purinergic signaling to modulate actin-cytoskeleton and cell contacts, which may be a functional link to NF2/Merlin.

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