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Title: Self-assembled monolayers to create novel surfaces utilising peptides identified by phage display for in vitro study of cancer stem cells
Author: O'Malley, C.
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2019
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Systematic analyses of global cancer rates suggest the annual number of head and neck cancer (HNC) cases is approaching 1 million and in England 5-year survival rates are remain around 50%. This is due to metastasis and recurrence which are thought to be driven by a subset of cells within the tumour with stem cell-like properties, so-called cancer stem cells (CSCs). Within HNC further sub-populations of CSCs with a mesenchymal phenotype have been identified. To better understand the role of these epithelial-to-mesenchymal transition (EMT) cells in cancer progression in vitro models are used. One rapid way of creating a system with a controlled surface environment for studying cell behaviour is to use self-assembled monolayers (SAMs). Here we use a peptide-based SAM to immobilise hyaluronic acid (HA), which plays a role in HNC progression, to create and characterise a model surface for studying the interaction with cells in vitro. This surface can support the culture of cancer cells and, when compared to existing methods of HA immobilisation, has different properties, including roughness and hydrophobicity and was seen to influence cell migration. In vitro use of HA-inspired glycopolymers was also assessed for their ability to mimic HA's effects on cancer cell behaviour, with a view to reducing the use of animal-derived HA. In parallel studies phage display was used to identify a peptide which showed enhanced binding to the EMT subset of CSCs. This peptide can then be used in the previously established SAM system to create a surface with the potential to probe cancer cell behaviour in a well-defined surface. Looking ahead this surface could be used for crude enrichment of the EMT fraction and determining the peptide's cell surface binding partner could provide an additional marker for FACS-based isolation of this population.
Supervisor: Not available Sponsor: Queen Mary Institute of Bioengineering ; Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: cancer stem cells ; head and neck cancer ; in vitro study