Abstract 385: Monocyte chemoattractant protein-1 (MCP-1)/CCL2 produced by non-tumor cells in tumor stroma promotes lung metastasis of 4T1 murine breast cancer cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 2011-04, Vol.71 (8_Supplement), p.385-385
• Main Authors: Yoshimura, Teizo, Zack Howard, O. M., Matsukawa, Akihiro, Chen, Keqiang, Liu, Ying, Wang, Ji Ming, Oppenheim, Joost J.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-385

MCP-1 is a chemokine that plays an important role in the initiation and progression of cancer by attracting immunosuppressive macrophages. A wide variety of tumor cell lines produce MCP-1 in vitro; thus, tumor cells are considered to be the main source of this chemokine. In the present study, we examined whether MCP-1 deficiency in non-tumor cells present in tumor stroma affects the growth and metastasis of the 4T1 mouse breast cancer cells implanted into the mammary pad of wild-type (WT) or MCP-1-deficient mice. Tumors grew at a similar rate in both WT and MCP-1-deficient mice at the injected sites; however, the lung metastases were markedly reduced in MCP-1-deficient mice. Serum MCP-1 levels increased after 4T1 cell implantation in WT, but not in MCP-1-deficient mice. High levels of MCP-1 mRNA were detected in the mammary tumors of WT, but not of MCP-1-deficient mice, indicating that tumor cells were not the main source of MCP-1. In tumors of MCP-1-deficient mice, the infiltration of macrophages was reduced and the expression of cytokines, including IFN-γ, IL-4, IL-10 and IL-13, was elevated. Transplantation of MCP-1-deficient bone marrow cells into WT mice did not affect the number of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1-deficient mice significantly increased the lung metastasis. Finally, culture supernatants of 4T1 cells induced MCP-1 production in inflammatory macrophages. These results suggest that MCP-1 produced by non-tumor cells in tumor stroma, both bone marrow-derived and non-bone marrow-derived, facilitates lung metastasis of 4T1 cells by recruiting immunosuppressive macrophages. Thus, the inhibition of MCP-1 may be useful to reduce lung metastasis of breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 385. doi:10.1158/1538-7445.AM2011-385