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

S. Y.N. Jamaludin, I. Azimi, F. M. Davis, A. A. Peters, T. J. Gonda, E. W. Thompson, S. J. Roberts-Thomson, G. R. Monteith

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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.

Original languageEnglish
Pages (from-to)4289-4295
Number of pages7
JournalOncology Letters
Issue number4
Publication statusPublished - Apr 2018
Externally publishedYes


  • Breast cancer
  • Calcium signalling
  • Cluster of differentiation 24
  • CXC chemokine receptor type 4
  • CXC chemokine receptor type 7
  • Hypoxia-inducible factor 2α

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