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Title: Clonogenicity and stem cells
Author: Beaver, C. M.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Primary keratinocytes form 3 types of colony with different morphologies termed holoclones, meroclones and paraclones, thought to be derived from stem, early and late stage precursor cells respectively (Barrandon and Green, 1987b, Rochat et al., 1994). Cancer cell lines produce colonies with morphologies analogous to those of holoclones, meroclones and paraclones, and consequently holoclone morphology is used as a surrogate marker for stem cell colonies. The aim of this study was to elucidate the relationship between clonogenicity, colony morphology and stem cells. Colonies formed by primary prostate epithelial cells and prostate cancer cell lines (DU145, PC3, LNCaP) were characterised. The proportions of colonies were not altered significantly by modification of culture conditions. In contrast to cancer cells, primary prostate epithelial cells form only two types of colony, termed types 1 and 2, which are analogous to holoclones and paraclones. Only type 1 colonies were highly proliferative, able to self-renew and express putative stem cell markers. Paradoxically, cells from DU145 meroclones formed holoclones and had self-renewal capacity (by serial cloning and xenografting). It is concluded that the major difference between holoclone and meroclone colonies from the cancer cell line DU145 is the proportion of stem cells within each colony, not the presence or absence of stem cells. Phage display was used to look for targets on the surface of cells in Type 1 colonies. Various experimental protocols were tested, but no targets were identified.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available