10779/rcsi.10800263.v1
Simona Donatello
Simona
Donatello
Lance Hudson
Lance
Hudson
David C. Cottell
David C.
Cottell
Alfonso Blanco
Alfonso
Blanco
Igor Aurrekoetxea
Igor
Aurrekoetxea
Martin J. Shelly
Martin J.
Shelly
Peter A. Dervan
Peter A.
Dervan
Malcolm R. Kell
Malcolm R.
Kell
Maurice Stokes
Maurice
Stokes
Arnold DK Hill
Arnold DK
Hill
Ann M. Hopkins
Ann M.
Hopkins
An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models.
Royal College of Surgeons in Ireland
2019
Primary Culture
Breast Cancer
Senescence
Progenitor Cells
Ultrastructure
Surgery
2019-11-22 17:29:45
Journal contribution
https://repository.rcsi.com/articles/journal_contribution/An_imbalance_in_progenitor_cell_populations_reflects_tumour_progression_in_breast_cancer_primary_culture_models_/10800263
<p>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.</p>