Crosstalk between tumor cells and macrophages in stroma renders tumor cells as the primary source of MCP-1/CCL2 in Lewis lung carcinoma

Teizo Yoshimura, Mingyong Liu, Xin Chen, Liangzhu Li, Ji Ming Wang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma, and B16 melanoma, was stromal cells. In the present study, we identified that tumor cells were the primary source of MCP-1 in Lewis lung carcinoma (LLC), because MCP-1 mRNA was highly expressed in tumors grown in both wild type (WT) and MCP-1-/- mice with elevated serum MCP-1 levels. Since LLC cells isolated from tumors expressed low levels of MCP-1 in vitro, it appeared that the tumor-stromal cell interaction in a tumor microenvironment increased MCP-1 expression in LLC cells. In fact, co-culture of LLC cells with normal mouse peritoneal macrophages or normal lung cells containing macrophages increased MCP-1 expression by LLC cells. Macrophages from TNFα-/- mice failed to activate LLC cells and anti-TNFα neutralizing antibody abolished the effect of WT macrophages on LLC cells. When LLC cells were transplanted into TNFα-/- mice, the levels of MCP-1 mRNA in tumors and serum MCP-1 levels were markedly lower as compared to WT mice, and importantly, tumors grew more slowly. Taken together, our results indicate that TNFα released by tumor cell-activated macrophages is critical for increased MCP-1 production by tumors cells. Thus, disruption of tumor-stromal cell interaction may inhibit tumor progression by reducing the production of tumor-promoting proinflammatory mediators, such as MCP-1.

Original languageEnglish
Article number332
JournalFrontiers in immunology
Volume6
Issue numberJUN
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

Keywords

  • Chemokines
  • Inflammation
  • Lung cancer
  • Monocytes/macrophages
  • Tumor microenvironment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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