title: Induction of the MCP chemokine cluster cascade in the periphery by cancer cell-derived Ccl3.
abstract: The induction of localized pro-inflammatory niches in the periphery is instrumental in metastasis. In order to better understand how tumors engage distal sites and activate a pro-inflammatory response we utilized syngeneic breast cancers as a model and showed that soluble factors from the neoplastic epithelium activate the expression of the monocyte chemoattractive protein (MCP) chemokines of the mouse 11C cluster that include Ccl1, Ccl2, Ccl7, Ccl8, Ccl11 and Ccl12. Tissues such as the lungs and the brain, that are more prone to colonization by breast cancer cells, were more sensitive to MCP cluster chemokine induction than others such as the liver. Subsequent analyses involving chemokine arrays in breast cancer cells and media followed by functional validation assays in in vitro and in vivo identified the cytokine Ccl3 as the principle mediator of the communication between the neoplastic epithelium and the peripheral tissues in terms of MCP cluster chemokine induction. Our results show that MCP chemokines are activated in peripheral tissues of breast cancer-bearing mice, by a mechanism that involves breast cancer cell-derived Ccl3. Interference with the expression of cancer cell-derived Ccl3 may find application in the management of breast cancer metastases.
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, University of South Carolina, SC, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Farmaki
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, University of South Carolina, SC, USA.
authors.forename: Vimala
authors.initials: V
authors.lastname: Kaza
authors.affiliation: Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, SC, USA.
authors.forename: Ioulia
authors.initials: I
authors.lastname: Chatzistamou
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, University of South Carolina, SC, USA; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; Peromyscus Genetic Stock Center, University of South Carolina, SC, USA. Electronic address: kiarish@sccp.sc.edu.
authors.forename: Hippokratis
authors.initials: H
authors.lastname: Kiaris
mesh_terms: D000818:Animals; D054405:Chemokine CCL3 / Q000502:physiology*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis*; D041681:NIH 3T3 Cells; D009362:Neoplasm Metastasis
chemical_list: D054405:Chemokine CCL3; D018945:Monocyte Chemoattractant Proteins
keywords: Breast cancer; CCL3; Chemokine; Inflammation; Metastasis; Periphery