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

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-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. 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.

journal_name

J Exp Clin Cancer Res

authors

Donatello S,Hudson L,Cottell DC,Blanco A,Aurrekoetxea I,Shelly MJ,Dervan PA,Kell MR,Stokes M,Hill AD,Hopkins AM

doi

10.1186/1756-9966-30-45

subject

Has Abstract

pub_date

2011-04-26 00:00:00

pages

45

eissn

0392-9078

issn

1756-9966

pii

1756-9966-30-45

journal_volume

30

pub_type

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