Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation
Open Access
- 10 January 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 106 (3), 525-537
- https://doi.org/10.1038/bjc.2011.583
Abstract
Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood. 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. 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. 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.Keywords
This publication has 60 references indexed in Scilit:
- Mammographic morphology and distribution of calcifications in ductal carcinoma in situ diagnosed in organized screeningActa Radiologica, 2011
- Breast cancer cell migration is regulated through junctional adhesion molecule-A-mediated activation of Rap1 GTPaseBreast Cancer Research, 2011
- New relationships between breast microcalcifications and cancerBritish Journal of Cancer, 2010
- Characterisation of breast cancer cell lines and establishment of a novel isogenic subclone to study migration, invasion and tumourigenicityClinical & Experimental Metastasis, 2008
- Correlation of Mammographic Calcifications with HER-2/neu Overexpression in Primary Breast CarcinomasJournal of Digital Imaging, 2008
- VASCULAR CALCIFICATION IN PATIENTS WITH KIDNEY DISEASE: The Vascular Biology of CalcificationSeminars in Dialysis, 2007
- Comprehensive Identification of Post-translational Modifications of Rat Bone Osteopontin by Mass SpectrometryBiochemistry, 2005
- Vascular Calcification MechanismsJournal of the American Society of Nephrology, 2004
- β-Glycerophosphate Accelerates Calcification in Cultured Bovine Vascular Smooth Muscle CellsArteriosclerosis, Thrombosis, and Vascular Biology, 1995
- Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotypeEndocrine Reviews, 1993