IL-25 blockade inhibits metastasis in breast cancer

Protein Cell. 2017 Mar;8(3):191-201. doi: 10.1007/s13238-016-0345-7. Epub 2016 Dec 1.

Abstract

Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4+ T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.

Keywords: IL-25; MMTV-PyMT; breast cancer; metastasis.

MeSH terms

  • Animals
  • Antibodies, Neoplasm / pharmacology*
  • Antibodies, Neutralizing / pharmacology*
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Female
  • Humans
  • Interleukin-17* / antagonists & inhibitors
  • Interleukin-17* / genetics
  • Interleukin-17* / immunology
  • Interleukins* / antagonists & inhibitors
  • Interleukins* / genetics
  • Interleukins* / immunology
  • Macrophages / immunology
  • Macrophages / pathology
  • Mammary Neoplasms, Animal* / drug therapy
  • Mammary Neoplasms, Animal* / genetics
  • Mammary Neoplasms, Animal* / immunology
  • Mice
  • Neoplasm Metastasis
  • Tumor Microenvironment* / drug effects
  • Tumor Microenvironment* / genetics
  • Tumor Microenvironment* / immunology

Substances

  • Antibodies, Neoplasm
  • Antibodies, Neutralizing
  • IL25 protein, human
  • Interleukin-17
  • Interleukins
  • Mydgf protein, mouse