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Title: Investigating the properties of cancer stem cells and epithelial to mesenchymal transition in human prostate cancer
Author: Dunning-Foreman, N. L.
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2012
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In recent years, the cancer stem cell hypothesis has emerged as a compelling but controversial model of cancer progression. Contrary to the clonal evolution model, the cancer stem cell hypothesis postulates that, akin to normal tissues, tumours are hierarchical and only a rare subpopulation of cells, so-called “cancer stem cells” (CSCs), possess the unique biological properties required for tumourigenesis. In addition to tumour initiation, cancer stem cells are held solely accountable for tumour differentiation, tumour maintenance, tumour spread and tumour relapse following therapy. Of late, there has been much evidence to suggest that cancer cells reactivate the latent embryonic programme, epithelial to mesenchymal transition (EMT), in order to acquire the invasive and migratory properties necessary for the successful completion of the invasion-metastasis cascade. Intriguingly, the EMT programme was recently implicated in the generation of cells with the properties of stem cells in a breast cancer model, therefore, it is evident that multiple populations of CSCs may exist within a given tumour. Since metastasis is accountable for the vast majority of cancer-associated mortalities and CSCs are implicated in therapy failure and subsequent cancer relapse, it is apparent that epithelial to mesenchymal transition and cancer stem cells are of utmost clinical relevance. Consequently, this study sought to investigate the properties of CSCs and EMT in human prostate cancer. Using the method previously reported in the literature, this work failed to identify and isolate putative prostate CSCs. However, this study successfully identified the OPCT-1 cell line as a suitable model for the investigation of EMT and subsequently derived and selected five phenotypically distinct clones that provided a model to determine a possible correlation between EMT and the generation of CSCs in human prostate cancer. The present work revealed that EMT of prostate cancer cells does not always generate cells with the properties of stem cells. Furthermore, this study demonstrated evidence for the existence of multiple cancer stem cell-like populations in human prostate cancer. In addition, evidence of EMT in primary cultures and clinical specimens from prostate cancer patients was shown and evidence to suggest that tumours contribute to their own stromal microenvironment via EMT was also provided. The foundations laid by the completion of this project provide considerable scope for future studies which may reveal valuable insights into the fundamental mechanisms involved in prostate cancer progression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available