The acquisition of a metastatic phenotype in breast epithelial cells is a progressive process, influenced by a large variety of cellular and soluble factors. Of these, members of the
chemokine superfamily, such as CCL2, CCL5, CXCL8 and CXCL12 have been recently suggested to promote
breast cancer progression. A pre-requisite for elucidation of the role of other
chemokines in
breast cancer progression is the characterization of
chemokine and
chemokine receptor expression by
breast tumor cells. The present study focuses on CXCL10, a
CXC chemokine that was recently suggested to have anti-malignant properties, and its corresponding
receptor CXCR3. CXCR3 expression was detected in three human breast
adenocarcinoma cell lines, MDA-MB-231, MCF-7 and T47D. CXCR3 expression was potently up-regulated by growing the cells under stress conditions, imposed by serum
starvation. Unlike many other
chemokine receptors, CXCR3 expression was not down-regulated by exposure to high concentrations (500ng/ml) of its
ligand, CXCL10, but rather was promoted. CXCL10-induced up-regulation of CXCR3 expression in the three cell lines was inhibited by
cycloheximide, indicating that de novo
protein synthesis is required for this process. In addition to CXCR3, the secretion of CXCL10 was noted in the MDA-MB-231, MCF-7 and T47D cells. CXCL10 secretion was found to be down-regulated by
IL-6, a potentially pro-malignant
cytokine in
breast cancer. The concomitant expression of CXCR3 and CXCL10 in
breast tumor cells suggests that a CXCR3-CXCL10 axis may function in these cells, and paves the way for an in depth analysis of CXCL10-CXCR3 interactions in
breast tumor cells.