Peer Reviewed

1

Document Type

Article

Publication Date

24-1-2019

Keywords

Calcification, Physiologic, Osteoblasts, Matrix vesicles.

Funder/Sponsor

Breast Cancer Now grant 2013NovPhD147.

Comments

The original article is available at https://www.nature.com

Abstract

Microcalcifications are vital mammographic indicators contributing to the early detection of up to 50% of non-palpable tumours and may also be valuable as prognostic markers. However, the precise mechanism by which they form remains incompletely understood. Following development of an in vitro model using human breast cancer cells lines cultured with a combination of mineralisation-promoting reagents, analysis of calcium deposition, alkaline phosphatase (ALP) activity and changes in expression of key genes was used to monitor the calcification process. Two cell lines were identified as successfully mineralising in vitro, MDA-MB-231 and SKBR3. Mineralising cell lines displayed higher levels of ALP activity that was further increased by addition of mineralisation promoting media. qPCR analysis revealed changes in expression of both pro- (RUNX2) and anti- (MGP, ENPP1) mineralisation genes. Mineralisation was suppressed by chelation of intracellular Ca2+ and inhibition of TRPM7, demonstrating a functional role for the channel in formation of microcalcifications. Increased Mg2+ was also found to effectively reduce calcium deposition. These results expand the number of human breast cancer cell lines with a demonstrated in vitro mineralisation capability, provide further evidence for the role of an active, cellular process of microcalcification formation and demonstrate for the first time a role for TRPM7 mediated Ca2+ transport.

Disciplines

Life Sciences

Citation

O'Grady S, Morgan MP. Deposition of calcium in an in vitro model of human breast tumour calcification reveals functional role for ALP activity, altered expression of osteogenic genes and dysregulation of the TRPM7 ion channel. Scientific Reports. 2019;9(1):542.

PubMed ID

30679450

DOI Link

10.1038/s41598-018-36496-9

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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Life Sciences Commons

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