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

Abstract

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.

• Authors: Natalie Waldt, David Scharnetzki, Christoph Kesseler, Elmar Kirches, Nele Stroscher, Frank-D Böhmer, Christian Mawrin
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 408 Pg. 116553 (Jan 15 2020) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 31715329 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• NF2 protein, human
• Neurofibromin 2
• PTPRJ protein, human
• Receptor-Like Protein Tyrosine Phosphatases, Class 3

Topics

• Animals
• Animals, Newborn
• Cell Line, Tumor
• Humans
• Meningeal Neoplasms (genetics, metabolism, pathology)
• Meningioma (genetics, metabolism, pathology)
• Mice
• Mice, Transgenic
• Neurofibromin 2 (deficiency, genetics)
• Receptor-Like Protein Tyrosine Phosphatases, Class 3 (deficiency, genetics)