JOURNAL ARTICLE

Loss of PTPRJ/DEP-1 enhances NF2/Merlin-dependent meningioma development

Natalie Waldt, David Scharnetzki, Christoph Kesseler, Elmar Kirches, Nele Stroscher, Frank-D Böhmer, Christian Mawrin
Journal of the Neurological Sciences 2019 November 9, 408: 116553
31715329

INTRODUCTION: Meningiomas are common tumors in adults, which develop from the meningeal coverings of the brain and spinal cord. Loss-of-function mutations or deletion of the NF2 gene, resulting in loss of the encoded Merlin protein, lead to Neurofibromatosis type 2 (NF2), but also cause the formation of sporadic meningiomas. It was shown that inactivation of Nf2 in mice caused meningioma formation. Another meningioma tumor-suppressor candidate is the receptor-like density-enhanced phosphatase-1 (DEP-1), encoded by PTPRJ. Loss of DEP-1 enhances meningioma cell motility in vitro and invasive growth in an orthotopic xenograft model. Ptprj-deficient mice develop normally and do not show spontaneous tumorigenesis. Another genetic lesion may be required to interact with DEP-1 loss in meningioma genesis.

METHODS: In the present study we investigated in vitro and in vivo whether the losses of DEP-1 and Merlin/NF2 may have a combined effect.

RESULTS: Human meningioma cells deficient for DEP-1, Merlin/NF2 or both showed no statistically significant changes in cell proliferation, while DEP-1 or DEP1/NF2 deficiency led to moderately increased colony size in clonogenicity assays. In addition, the loss of any of the two genes was sufficient to induce a significant reduction of cell size (p < .05) and profound morphological changes. Most important, in Ptprj knockout mice Cre/lox mediated meningeal Nf2 knockout elicited a four-fold increased rate of meningioma formation within one year compared with mice with Ptprj wild type alleles (25% vs 6% tumor incidence).

CONCLUSIONS: Our data suggest that loss of DEP-1 and Merlin/NF2 synergize during meningioma genesis.

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