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

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.