Investigating the role of FGFR3 in quiescent glioma stem cells (GSCs)

Russell, Chloe 2025. Investigating the role of FGFR3 in quiescent glioma stem cells (GSCs). MPhil Thesis, Cardiff University. Item availability restricted.

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Abstract

When tackling the poor survival of patients with GBM, exploring the tumour at both the cellular and molecular level presents a new perspective of the aggressive and recurrent nature of this devastating disease. Considering the heterogeneity of GBM as a significant contributor to the success of the tumour; exploring the interactions between cell types and their tumour microenvironment may reveal nuances that evade current therapies. Cancer stem cells are defined as a cell subtype within a tumour with stem-like qualities that promote the success of the tumour itself. GSCs are considered heterogeneous in their ability to exist between different states of the cell cycle: proliferative, dormant and quiescent. Defining GSC quiescence in vivo is challenging due to a reduced population of cells concerned and the complexity of the environment in situ. GSC cell state may be influenced by extracellular interactions between the GSCs and the tumour microenvironment. FGFRs are a family of cell surface tyrosine kinase receptors that are over expressed in infiltrating GBM cells and are associated with tumorigenesis and tumour growth. With previous studies having demonstrated the role of FGFR1 in promoting stemness at the invasive front of the tumour, and FGFR2 expression primarily in the tumour mass; the role of FGFR3 within the tumour has not yet been fully explored. This study aims to explore this firstly by determining whether FGFR3 expression is associated with quiescence in GBM; and secondly to investigate the mechanisms of cellular quiescence in FGFR3 positive human GBM cells. Current studies implicate interactions between FGFR3 and its microenvironment in the influence of cancer stem cell quiescence, via an induced quiescence using BMP4. Building on these current studies in NSCs, one may develop assays that investigate the cell state of human GBM cell lines. To do this, BMP4 was used to induce cell differentiation, and growth factors to assess how BMP4 treatment affects the ability of cells to re-enter replicative states. Following BMP4 treatment, GBM cells show induced quiescent conditions, demonstrated by cell cycle exit and over expression of quiescent markers. Using this culture system to investigate the role of FGFR3 on quiescent cell states, it was established that FGFR3 is overexpressed in cells treated with BMP4 after 3 days, with further 8 analysis associating FGFR3 with retained stemness, but a slower proliferative ability, which might suggest a positive correlation between FGFR3 expression and quiescence.

Item Type:	Thesis (MPhil)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	22 May 2026
Last Modified:	22 May 2026 13:34
URI:	https://orca.cardiff.ac.uk/id/eprint/187173

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