Use this URL to cite or link to this record in EThOS:
Title: Comparison of the DNA damage response and mechanisms of treatment resistance in stem cells originating from malignant and benign prostate tissues and their differentiated counterparts
Author: Klein, Sandra
ISNI:       0000 0004 2733 2005
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2013
Availability of Full Text:
Access from EThOS:
Access from Institution:
Prostate cancer is the most frequently diagnosed malignant disorder in men and despite intensive research there is little effective therapy against tumour recurrence and metastatic disease. Recent findings direct the origins of prostate cancer to cancer stem cells (CSCs). The CSC model proposes that tumours are hierarchically organized and sustained by CSCs that act as an undifferentiated reservoir within the tumour. Similar to their normal counterparts, CSCs are thought to be highly protected against DNA damage, which might play a crucial role in therapy failure and tumour recurrence. Our findings indicate that CD133+/α2β1integrin^high stem cells (SCs) from malignant and benign prostate tissues are more effectively protected against DNA damage introduced by etoposide than CD133-/α2β1integrin^high transit amplifying (TAs) and CD133-/α2β1integrin^low committed basal cells (CBs). Furthermore, the colony forming efficiency in prostate SCs was less affected by the drug. The assessment of ABC-transporters revealed that these are unlikely to be mediators of the enhanced resistance in SCs. However, according to a cell cycle analysis a higher proportion of SCs was quiescent when compared to TA or CB populations. Hence, cellular dormancy might be one factor contributing to therapy survival. Further research is required to determine the role of CSCs in treatment resistance. Future therapies that target specifically prostate CSCs might be a key to prevent tumour relapse.
Supervisor: Meuth, Mark Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available