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

Hdl Handle:
http://hdl.handle.net/10147/139353
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 D K; Hopkins, Ann M
Affiliation:
Department of Surgery, Royal College of Surgeons in Ireland; Dublin, Ireland.
Citation:
An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models. 2011, 30:45 J. Exp. Clin. Cancer Res.
Journal:
Journal of experimental & clinical cancer research : CR
Issue Date:
2011
URI:
http://hdl.handle.net/10147/139353
DOI:
10.1186/1756-9966-30-45
PubMed ID:
21521500
Abstract:
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.; 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.; 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-tumorigenic 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.; 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:
Article
Language:
en
MeSH:
Actins; Breast Neoplasms; Cell Aging; Cell Culture Techniques; Cell Proliferation; Cell Shape; Female; Humans; Keratins, Type I; Membrane Proteins; Neoplastic Stem Cells; Tumor Cells, Cultured; Tumor Markers, Biological; Vimentin
ISSN:
1756-9966

Full metadata record

DC FieldValue Language
dc.contributor.authorDonatello, Simonaen
dc.contributor.authorHudson, Lanceen
dc.contributor.authorCottell, David Cen
dc.contributor.authorBlanco, Alfonsoen
dc.contributor.authorAurrekoetxea, Igoren
dc.contributor.authorShelly, Martin Jen
dc.contributor.authorDervan, Peter Aen
dc.contributor.authorKell, Malcolm Ren
dc.contributor.authorStokes, Mauriceen
dc.contributor.authorHill, Arnold D Ken
dc.contributor.authorHopkins, Ann Men
dc.date.accessioned2011-08-10T15:40:21Z-
dc.date.available2011-08-10T15:40:21Z-
dc.date.issued2011-
dc.identifier.citationAn imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models. 2011, 30:45 J. Exp. Clin. Cancer Res.en
dc.identifier.issn1756-9966-
dc.identifier.pmid21521500-
dc.identifier.doi10.1186/1756-9966-30-45-
dc.identifier.urihttp://hdl.handle.net/10147/139353-
dc.description.abstractMany 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.-
dc.description.abstractPrimary 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.-
dc.description.abstractSignificant 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-tumorigenic 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.-
dc.description.abstractOur results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.-
dc.language.isoenen
dc.subject.meshActins-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCell Aging-
dc.subject.meshCell Culture Techniques-
dc.subject.meshCell Proliferation-
dc.subject.meshCell Shape-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshKeratins, Type I-
dc.subject.meshMembrane Proteins-
dc.subject.meshNeoplastic Stem Cells-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshTumor Markers, Biological-
dc.subject.meshVimentin-
dc.titleAn imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.en
dc.typeArticleen
dc.contributor.departmentDepartment of Surgery, Royal College of Surgeons in Ireland; Dublin, Ireland.en
dc.identifier.journalJournal of experimental & clinical cancer research : CRen

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