Hopkins, Jack Douglas;
(2023)
The multifaceted role of PRELP in the regulation of retinoblastoma progression.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Small leucine-rich proteoglycans are secreted proteins that organise extracellular matrices and stipulate appropriate cellular signalling to maintain tissue homeostasis. Loss of these proteoglycans results in unsolicited signalling events that can trigger a wide range of diseases. The Ohnuma laboratory has previously found that PRELP, a class II small leucine-rich proteoglycan, is suppressed in a range of different cancers, including retinoblastoma. Thus, we hypothesised that PRELP may have tumour suppressive properties that inhibit retinoblastoma progression. To this end, we employed two approaches: mRNA expression profiling of a Prelp-/- mouse model and PRELP-treated retinoblastoma cell lines; and in vitro functional analysis of retinoblastoma cells treated with PRELP. Our ontological analysis of the mRNA profile of Prelp-/- mice strongly correlated with many cancer characteristics. Pathways involved in cell-cell and cell-ECM adhesion, microenvironment architecture and oncogenic signalling such as TGBβ1, EGF, WNT3A, IL6 and TNFα were upregulated. Conversely, a large number of these pathways were suppressed in PRELP-treated retinoblastoma cells. We hypothesised that these changes in gene expression may correlate to a reduction in the cancer phenotype of retinoblastoma cells in vitro. Indeed, we found that PRELP activated apoptosis and suppressed proliferation under different conditions. PRELP also acted as a pan-activator of adhesion compounds. Overall, we improved the understanding of PRELP tumour suppressive properties and demonstrated that addition of PRELP can diminish retinoblastoma progression. We conclude that integration of PRELP treatment could improve current therapeutic treatment strategies for retinoblastoma.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The multifaceted role of PRELP in the regulation of retinoblastoma progression |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10174317 |
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