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Assessment of CXC ligand 12-mediated calcium signalling and its regulators in basal-like breast cancer cells.

Assessment of CXC ligand 12-mediated calcium signalling and its regulators in basal-like breast cancer cells.
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Jamaludin SYN, Azimi I, Davis FM, Peters AA, Gonda TJ, Thompson EW, Roberts-Thomson SJ, Monteith GR,


Jamaludin SYN, Azimi I, Davis FM, Peters AA, Gonda TJ, Thompson EW, Roberts-Thomson SJ, Monteith GR, (click to view)

Jamaludin SYN, Azimi I, Davis FM, Peters AA, Gonda TJ, Thompson EW, Roberts-Thomson SJ, Monteith GR,

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Oncology letters 2018 01 1915(4) 4289-4295 doi 10.3892/ol.2018.7827

Abstract

CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Casignalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Caresponses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells. Cluster of differentiation (CD)24, the negative regulator of CXCL12 responses, demonstrated increased expression in MDA-MB-468 cells compared with MDA-MB-231 cells, and the two cell lines expressed comparable levels of hypoxia-inducible factor (HIF)2α, a CXCR4 regulator. Induction of epithelial-mesenchymal transition (EMT) by epidermal growth factor exhibited opposite effects on CXCR4 mRNA levels compared with hypoxia-induced EMT. Neither EMT inducer exhibited an effect on CXCR7 expression, however hypoxia increased HIF2α expression levels in MDA-MB-468 cells. Analysis of the gene expression profiles of breast tumours revealed that the highest expression levels of CXCR4 and CXCR7 were in the Claudin-Low molecular subtype, which is markedly associated with EMT features.

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