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Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation.

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posted on 22.11.2019 by Rachel F. Cox, Aron Hernandez-Santana, S Ramdass, Gillian McMahon, Judith H. Harmey, Maria P. Morgan

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.

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.

Funding

Royal College of Surgeons in Ireland Research Committee

History

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The original article is available at www.bjcancer.com

Published Citation

Cox RF, Hernandez-Santana A, Ramdass S, McMahon G, Harmey JH, Morgan MP. Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation. British Journal of Cancer. 2012;106(3):525-37

Publication Date

31/01/2012

Publisher

Cancer Research UK

PubMed ID

22233923

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