title: Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation.
abstract: BACKGROUND
  Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood.
  
  
  METHODS
  We report a novel model to investigate the in vitro mineralisation potential of a panel of mammary cell lines. Primary mammary tumours were produced by implanting tumourigenic cells into the mammary fat pads of female BALB/c mice.
  
  
  RESULTS
  Hydroxyapatite (HA) was deposited only by the tumourigenic cell lines, indicating mineralisation potential may be associated with cell phenotype in this in vitro model. We propose a mechanism for mammary mineralisation, which suggests that the balance between enhancers and inhibitors of physiological mineralisation are disrupted. Inhibition of alkaline phosphatase and phosphate transport prevented mineralisation, demonstrating that mineralisation is an active cell-mediated process. Hydroxyapatite was found to enhance in vitro tumour cell migration, while calcium oxalate had no effect, highlighting potential consequences of calcium deposition. In addition, HA was also deposited in primary mammary tumours produced by implanting the tumourigenic cells into the mammary fat pads of female BALB/c mice.
  
  
  CONCLUSIONS
  This work indicates that formation of mammary HA is a cell-specific regulated process, which creates an osteomimetic niche potentially enhancing breast tumour progression. Our findings point to the cells mineralisation potential and the microenvironment regulating it, as a significant feature of breast tumour development.
authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
authors.forename: R F
authors.initials: RF
authors.lastname: Cox
authors.forename: A
authors.initials: A
authors.lastname: Hernandez-Santana
authors.forename: S
authors.initials: S
authors.lastname: Ramdass
authors.forename: G
authors.initials: G
authors.lastname: McMahon
authors.forename: J H
authors.initials: JH
authors.lastname: Harmey
authors.forename: M P
authors.initials: MP
authors.lastname: Morgan
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002114:Calcinosis / Q000473:pathology*; D002119:Calcium Carbonate / Q000378:metabolism; D002129:Calcium Oxalate / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D017886:Durapatite / Q000378:metabolism; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010710:Phosphates / Q000378:metabolism
chemical_list: D010710:Phosphates; D002129:Calcium Oxalate; D017886:Durapatite; D000469:Alkaline Phosphatase; D002119:Calcium Carbonate