title: The expression of the chemokine receptor CXCR3 and its ligand, CXCL10, in human breast adenocarcinoma cell lines.
abstract: 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.
authors.affiliation: Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Lilach
authors.initials: L
authors.lastname: Goldberg-Bittman
authors.forename: Eran
authors.initials: E
authors.lastname: Neumark
authors.forename: Orit
authors.initials: O
authors.lastname: Sagi-Assif
authors.forename: Elina
authors.initials: E
authors.lastname: Azenshtein
authors.forename: Tsipi
authors.initials: T
authors.lastname: Meshel
authors.forename: Isaac P
authors.initials: IP
authors.lastname: Witz
authors.forename: Adit
authors.initials: A
authors.lastname: Ben-Baruch
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism*; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine