Studying biomineralization pathways in a 3D culture model of breast cancer microcalcifications

Microcalcifications serve as diagnostic markers for breast cancer, yet their formation pathway(s) and role in cancer progression are debated due in part to a lack of relevant 3D culture models that allow studying the extent of cellular regulation over mineralization. Previous studies have suggested...

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Bibliographic Details
Published in:Biomaterials 2018-10, Vol.179, p.71-82
Main Authors: Vidavsky, Netta, Kunitake, Jennie AMR, Chiou, Aaron E., Northrup, Paul A., Porri, Teresa J., Ling, Lu, Fischbach, Claudia, Estroff, Lara A.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
alkaline phosphatase
apatite
biomineralization
breast neoplasms
cell death
cell lines
cell viability
disease course
Ductal carcinoma in situ
electron microscopy
humans
Multicellular spheroids
neoplasm cells
osteopontin
Pathological mineralization
spectroscopy
X-radiation
XANES
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Summary:Microcalcifications serve as diagnostic markers for breast cancer, yet their formation pathway(s) and role in cancer progression are debated due in part to a lack of relevant 3D culture models that allow studying the extent of cellular regulation over mineralization. Previous studies have suggested processes ranging from dystrophic mineralization associated with cell death to bone-like mineral deposition. Here, we evaluated microcalcification formation in 3D multicellular spheroids, generated from non-malignant, pre-cancer, and invasive cell lines from the MCF10A human breast tumor progression series. The spheroids with greater malignancy potential developed necrotic cores, thus recapitulating spatially distinct viable and non-viable areas known to regulate cellular behavior in tumors in vivo. The spatial distribution of the microcalcifications, as well as their compositions, were characterized using nanoCT, electron-microscopy, and X-ray spectroscopy. Apatite microcalcifications were primarily detected within the viable cell regions and their number and size increased with malignancy potential of the spheroids. Levels of alkaline phosphatase decreased with malignancy potential, whereas levels of osteopontin increased. These findings support a mineralization pathway in which cancer cells induce mineralization in a manner that is linked to their malignancy potential, but that is distinct from physiological osteogenic mineralization.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2018.06.030