PMID- 26834744 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160202 LR - 20181113 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 7 DP - 2016 TI - Induction of Monocyte Chemoattractant Proteins in Macrophages via the Production of Granulocyte/Macrophage Colony-Stimulating Factor by Breast Cancer Cells. PG - 2 LID - 10.3389/fimmu.2016.00002 [doi] LID - 2 AB - Monocyte chemoattractant protein-1 (MCP-1)/CCL2 plays an important role in the initiation and progression of cancer. We previously reported that in 4T1 murine breast cancer, non-tumor stromal cells, including macrophages, were the major source of MCP-1. In the present study, we analyzed the potential mechanisms by which MCP-1 is upregulated in macrophages infiltrating 4T1 tumors. We found that cell-free culture supernatants of 4T1 cells (4T1-sup) markedly upregulated MCP-1 production by peritoneal inflammatory macrophages. 4T1-sup also upregulated other MCPs, such as MCP-3/CCL7 and MCP-5/CCL12, but modestly upregulated neutrophil chemotactic chemokines, such as KC/CXCL1 or MIP-2/CXCL2. Physicochemical analysis indicated that an approximately 20-30 kDa 4T1 cell product was responsible for the capacity of 4T1-sup to upregulate MCP-1 expression by macrophages. A neutralizing antibody against granulocyte/macrophage colony-stimulating factor (GM-CSF), but not macrophage CSF, almost completely abrogated MCP-1-inducing activity of 4T1-sup, and recombinant GM-CSF potently upregulated MCP-1 production by macrophages. The expression levels of GM-CSF in 4T1 tumors in vivo were higher than other tumors, such as Lewis lung carcinoma. Treatment of mice with anti-GM-CSF antibody significantly reduced the growth of 4T1 tumors at the injection sites but did not reduce MCP-1 production or lung metastasis in tumor-bearing mice. These results indicate that 4T1 cells have the capacity to directly upregulate MCP-1 production by macrophages by releasing GM-CSF; however, other mechanisms are also involved in increased MCP-1 levels in the 4T1 tumor microenvironment. FAU - Yoshimura, Teizo AU - Yoshimura T AD - Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA; Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Imamichi, Tomozumi AU - Imamichi T AD - Laboratory of Human Retrovirology and Immunoinformatics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research , Frederick, MD , USA. FAU - Weiss, Jonathan M AU - Weiss JM AD - Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick, MD , USA. FAU - Sato, Miwa AU - Sato M AD - Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University , Okayama , Japan. FAU - Li, Liangzhu AU - Li L AD - Engineering Research Center for Cell and Therapeutic Antibody of Ministry of Education, School of Pharmacy, Shanghai Jiaotong University , Shanghai , China. FAU - Matsukawa, Akihiro AU - Matsukawa A AD - Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University , Okayama , Japan. FAU - Wang, Ji Ming AU - Wang JM AD - Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick, MD , USA. LA - eng GR - HHSN261200800001C/RC/CCR NIH HHS/United States GR - HHSN261200800001E/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20160120 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 EIN - Front Immunol. 2017 Nov 13;8:1524. PMID: 29151836 PMC - PMC4718995 OTO - NOTNLM OT - breast cancer OT - chemokines OT - inflammation OT - monocytes/macrophages OT - tumor microenvironment EDAT- 2016/02/03 06:00 MHDA- 2016/02/03 06:01 PMCR- 2016/01/01 CRDT- 2016/02/03 06:00 PHST- 2015/08/11 00:00 [received] PHST- 2016/01/05 00:00 [accepted] PHST- 2016/02/03 06:00 [entrez] PHST- 2016/02/03 06:00 [pubmed] PHST- 2016/02/03 06:01 [medline] PHST- 2016/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2016.00002 [doi] PST - epublish SO - Front Immunol. 2016 Jan 20;7:2. doi: 10.3389/fimmu.2016.00002. eCollection 2016.