An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

Hdl Handle:
http://hdl.handle.net/10147/129536
Title:
An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models
Authors:
Donatello, Simona; Hudson, Lance; Cottell, David C; Blanco, Alfonso; Aurrekoetxea, Igor; Shelly, Martin J; Dervan, Peter A; Kell, Malcolm R; Stokes, Maurice; Hill, Arnold DK; Hopkins, Ann M
Citation:
Journal of Experimental & Clinical Cancer Research. 2011 Apr 26;30(1):45
Issue Date:
26-Apr-2011
URI:
http://hdl.handle.net/10147/129536
Abstract:
Abstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.
Item Type:
Journal Article

Full metadata record

DC FieldValue Language
dc.contributor.authorDonatello, Simona-
dc.contributor.authorHudson, Lance-
dc.contributor.authorCottell, David C-
dc.contributor.authorBlanco, Alfonso-
dc.contributor.authorAurrekoetxea, Igor-
dc.contributor.authorShelly, Martin J-
dc.contributor.authorDervan, Peter A-
dc.contributor.authorKell, Malcolm R-
dc.contributor.authorStokes, Maurice-
dc.contributor.authorHill, Arnold DK-
dc.contributor.authorHopkins, Ann M-
dc.date.accessioned2011-05-13T15:17:43Z-
dc.date.available2011-05-13T15:17:43Z-
dc.date.issued2011-04-26-
dc.identifierhttp://dx.doi.org/10.1186/1756-9966-30-45-
dc.identifier.citationJournal of Experimental & Clinical Cancer Research. 2011 Apr 26;30(1):45-
dc.identifier.urihttp://hdl.handle.net/10147/129536-
dc.description.abstractAbstract Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.-
dc.titleAn imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models-
dc.typeJournal Article-
dc.language.rfc3066en-
dc.rights.holderDonatello et al.; licensee BioMed Central Ltd.-
dc.description.statusPeer Reviewed-
dc.date.updated2011-05-13T10:04:27Z-
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