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>