Assessment of CXC ligand 12-mediated calcium signalling and its regulators in basal-like breast cancer cells
Date
2018
Authors
Jamaludin, S.Y.N.
Azimi, I.
Davis, F.M.
Peters, A.A.
Gonda, T.J.
Thompson, E.W.
Roberts Thomson, S.J.
Monteith, G.R.
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Journal article
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Oncology Letters, 2018; 15(4):4289-4295
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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 Ca2+signalling 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 Ca2+responses 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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Copyright 2018 Jamaludin et al. This work is licensed under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) License. (https://creativecommons.org/licenses/by-nc-nd/4.0/)