Peer Reviewed

1

Document Type

Article

Publication Date

26-4-2011

Keywords

Primary Culture, Breast Cancer, Senescence, Progenitor Cells, Ultrastructure

Comments

This article is also available from http://www.jeccr.com/content/pdf/1756-9966-30-45

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.

Disciplines

Surgery

Citation

Donatello S, Hudson L, Cottell DC, Blanco A, Aurrekoetxea I, Shelly MJ, Dervan PA, Kell MR, Stokes M, Hill ADK, Hopkins AM. An imblance in progenitor cell populations reflects tumour progression in breast cancer primary culture models. Journal of Experimental and Clinical Cancer Research. 2011;30(1);45.

PubMed ID

21521500

DOI Link

10.1186/1756-9966-30-45

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Surgery Commons

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