Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation.
Rachel F. Cox
Aron Hernandez-Santana
S Ramdass
Gillian McMahon
Judith H. Harmey
Maria P. Morgan
10779/rcsi.10783511.v1
https://repository.rcsi.com/articles/journal_contribution/Microcalcifications_in_breast_cancer_novel_insights_into_the_molecular_mechanism_and_functional_consequence_of_mammary_mineralisation_/10783511
<p>BACKGROUND: Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood.</p>
<p>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.</p>
<p>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.</p>
<p>CONCLUSION: 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.</p>
2019-11-22 16:24:32
Adenocarcinoma
Alkaline Phosphatase
Animals
Breast Neoplasms
Calcinosis
Calcium Carbonate
Calcium Oxalate
Cell Line
Tumor
Cell Transformation
Neoplastic
Durapatite
Female
Mammary Neoplasms
Experimental
Mice
Inbred BALB C
Phosphates
Clinical Pharmacology and Therapeutics