title: 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.
authors.affiliation: Department of Surgery, Royal College of Surgeons in Ireland; Dublin, Ireland.
authors.forename: Simona
authors.initials: S
authors.lastname: Donatello
authors.forename: Lance
authors.initials: L
authors.lastname: Hudson
authors.forename: David C
authors.initials: DC
authors.lastname: Cottell
authors.forename: Alfonso
authors.initials: A
authors.lastname: Blanco
authors.forename: Igor
authors.initials: I
authors.lastname: Aurrekoetxea
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Shelly
authors.forename: Peter A
authors.initials: PA
authors.lastname: Dervan
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Kell
authors.forename: Maurice
authors.initials: M
authors.lastname: Stokes
authors.forename: Arnold D K
authors.initials: AD
authors.lastname: Hill
authors.forename: Ann M
authors.initials: AM
authors.lastname: Hopkins
mesh_terms: D000199:Actins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D048430:Cell Shape; D016922:Cellular Senescence; D005260:Female; D006801:Humans; D053530:Keratins, Type I / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; D053530:Keratins, Type I; D008565:Membrane Proteins; D014746:Vimentin; C106354:flotillins