Mouse Models in Meningioma Research: A Systematic Review

Abstract

Meningiomas are the most frequent primitive central nervous system tumors found in adults. Mouse models of cancer have been instrumental in understanding disease mechanisms and establishing preclinical drug testing. Various mouse models of meningioma have been developed over time, evolving in light of new discoveries in our comprehension of meningioma biology and with improvements in genetic engineering techniques. We reviewed all mouse models of meningioma described in the literature, including xenograft models (orthotopic or heterotopic) with human cell lines or patient derived tumors, and genetically engineered mouse models (GEMMs). Xenograft models provided useful tools for preclinical testing of a huge range of innovative drugs and therapeutic options, which are summarized in this review. GEMMs offer the possibility of mimicking human meningiomas at the histological, anatomical, and genetic level and have been invaluable in enabling tumorigenesis mechanisms, including initiation and progression, to be dissected. Currently, researchers have a range of different mouse models that can be used depending on the scientific question to be answered.

Gene replacement therapy in a schwannoma mouse model of neurofibromatosis type 2

“… 39 Other mouse orthotopic allograft schwannoma models are also available. 40 , 41 It will be important to evaluate whether overexpression of merlin using an AAV vector can inhibit growth of schwannomas without mutations in NF2 , and other types of meningiomas 42 and ependymomas 43 in mouse models. There may also be ways to expand the effectiveness of this therapeutic paradigm by promoting the transfer of merlin via EVs or by injecting the vector into biofluids with broader access to tumors throughout the body, including intravenous and intrathecal injections.…”

Modeling Brain Tumors: A Perspective Overview of in vivo and Organoid Models

“…Meningioma is another common type of tumors located in the brain, which originates from the meninges. Meningiomas, representing the most frequent tumor in the adult, are generally benign (WHO Grade I) with a lower percentage classified as atypical (WHO Grade II) and rarely anaplastic (WHO Grade III) ( Boetto et al, 2021 ). The genomic profile of a large cohort of meningiomas has identified alteration in the genes encoding for NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog pathways ( Youngblood et al, 2019 ).…”

“…The genomic profile of a large cohort of meningiomas has identified alteration in the genes encoding for NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog pathways ( Youngblood et al, 2019 ). The mouse model of meningiomas consisted in xenograft of immortalized cell lines or patient-derived tumor cells ( McCutcheon et al, 2000 ; Püttmann et al, 2005 ; Cargioli et al, 2007 ; Ragel et al, 2008 ), GEMMs ( Kalamarides et al, 2002 , 2011 ; Peyre et al, 2013 , 2015 ; Boetto et al, 2018 , 2021 ) and syngeneic allogenic graft ( Boetto et al, 2021 ) ( Table 1 ). Meningiomas can be induced in GEMMs overexpressing PDGFB in a context of loss of function of Nf2 , Cdkn2ab or p16Ink4a or over-expressing only SmoM2 PGDS + arachnoid cells.…”

Malignant meningioma

“…With the current progress in murine meningioma models, frameworks for systematic target testing are increasingly available. 312 Results from targeting of mutations in NF2-dependent and NF2-independent meningiomas (clinical trial NCT02523014) are expected in October 2024. These drugs, if effective in recurrent meningioma, could be combined with drugs that target certain upregulated pathways in high-grade meningioma, for example a FAK-inhibitor (downstream NF2) combined with an EZH2 inhibitor (catalytic subunit of HOTAIR regulatory pathway).…”

“…In 2 years, four WHO grade 3 meningiomas and a corresponding or higher number of WHO grade 1 or 2 meningiomas could be included, resulting in a comprehensive single-cell dataset. Moreover, such a setup could produce meningioma samples for the development of patient-derived cell cultures, organoids 308,314 or orthotopic xenograft models 312 and subsequent pharmacological testing of potential targets.…”