Sanders, Ilson (2022) The role of extracellular vesicles in premetastatic niche formation as well as their value as metastatic biomarkers. Master's Thesis / Essay, Biomedical Sciences.
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Abstract
Metastasis is defined as the occurrence of secondary cancerous growths appearing elsewhere in the body away from the initial site of the primary tumour, and is well established to considerably and negatively affect disease outcome. Metastatic formation in a foreign host-tissue is preceded by a state of hiked susceptibility to cancerous dissemination. Such a tissue is referred to as a premetastatic niche (PMN). A group of cell secreted lipid enclosed packages containing proteins, RNA and DNA termed extracellular vesicles (EV) have been observed to play an extensive role in PMN formation. The aim of this thesis is to explore the contemporary understanding of the involvement of EVs in PMN formation, and from there judge the feasibility of using EVs to gauge metastatic risk in patients. EVs are known to both transmit and represent their parent cell’s phenotype. The primary tumour benefits evolutionary from immune suppression, angiogenesis, vascular leakage and extracellular matrix alterations. EVs evoking such modifications may land elsewhere in the body whereafter they give rise to metastases in four consecutive steps of tissue remodification: priming, licensing, initiation and progression. For these steps to occur immune suppression needs to be elicited by inhibiting and activating anti- and protumoral processes respectively, whereas EV-related markers indicating the exact opposite may be an indication of a better prognosis. Meanwhile, EV markers for angiogenesis and leaky vasculature may signify enhanced metastatic potential. As do those aimed at the deposition or breakdown of specific extracellular matrix components. Methods aimed at EV isolation and the acquisition of big data such as genomic, transcriptomic and proteomic data are being optimised. It is expected that the mechanisms underlying PMN formation will be further unravelled whilst extensive screening of EVs in patients gradually will become possible. When science and healthcare have arrived at that point, I propose establishing a metastatic potential staging system onto which personalised treatment could be based to negate metastatic risk.
| Item Type: | Thesis (Master's Thesis / Essay) |
|---|---|
| Supervisor name: | Kruyt, F.A.E. |
| Degree programme: | Biomedical Sciences |
| Thesis type: | Master's Thesis / Essay |
| Language: | English |
| Date Deposited: | 28 Jul 2022 11:56 |
| Last Modified: | 02 Aug 2022 08:03 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/27956 |
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