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2019 ; 9
(1
): 542
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English Wikipedia
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
#MMPMID30679450
O'Grady S
; Morgan MP
Sci Rep
2019[Jan]; 9
(1
): 542
PMID30679450
show ga
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 Ca(2+) and inhibition of TRPM7, demonstrating a functional role for
the channel in formation of microcalcifications. Increased Mg(2+) 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 Ca(2+) transport.