ORCID

Abstract

Although schwannomas and meningiomas are generally benign and slow-growing, the mass effect of either tumour within the nervous system causes life-altering symptoms. Individuals with NF2-related schwannomatosis may develop schwannomas and meningiomas, increasing tumour burden. The primary treatment for large or symptomatic schwannomas and meningiomas is surgical resection, which may not be suitable in cases involving tumours located near sensitive neuroanatomy or clinically vulnerable individuals. Not all schwannomas and meningiomas respond to alternative targeted treatments such as stereotactic radiosurgery or the vascular endothelial growth factor inhibitor bevacizumab. The main objective of this thesis was to investigate targeting of the receptor tyrosine kinase MERTK as a potential pharmacological intervention in schwannomas and meningiomas. Immunofluorescence and flow cytometry demonstrated that MERTK is expressed by tumour cells and macrophages in both tumour types. Western blot indicated that protein levels of MERTK, as well as macrophage markers CD163 and CD68, are highest in passage zero of schwannoma and meningioma primary cells. Drug treatment and immunocytochemistry experiments revealed that inhibition of MERTK by the small-molecule inhibitor UNC2025 reduces the number of tumour cells and macrophages present in schwannoma and meningioma cell cultures, simultaneously decreasing proliferation and increasing apoptosis in both cell types. These findings identify MERTK as a promising target for further pre-clinical investigations as a potential pharmacological intervention for schwannomas and meningiomas.

Awarding Institution(s)

University of Plymouth

Supervisor

Sylwia Ammoun, Oliver Hanemann, Gyorgy Fejer

Keywords

Schwannoma, Meningioma, Macrophages, Tumour Microenvironment

Document Type

Thesis

Publication Date

2025

Embargo Period

2025-11-14

Deposit Date

November 2025

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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