Interleukin-17, produced by lymphocytes, promotes tumor growth and angiogenesis in a mouse model of breast cancer

Mol Med Rep. 2012 Nov;6(5):1099-102. doi: 10.3892/mmr.2012.1036. Epub 2012 Aug 16.

Abstract

Previous studies have suggested that interleukin-17 (IL-17), an inflammatory cytokine expressed predominantly by Th17 cells, is highly expressed in tumor tissue and may help tumors to evade immune surveillance. In this study, the significance of IL-17 expression in the tumors of murine models of breast cancer was explored. BALB/c mice were injected with MA782/5S28102 or 4T1 breast cancer cell lines to establish breast tumors. The expression of IL-17 in tumor tissue was detected by western blotting 1 and 4 weeks later, which revealed that it increased with tumor progression (P<0.05). Additionally, tumor cells and tumor-infiltrating lymphocytes were isolated from tumor tissues and cultured for 5 days with stimulation by phorbol-12-myristate-13-acetate (PMA), anti‑CD3 antibody and anti-CD28 antibody. Culture media from stimulated tumor cells or tumor-infiltrating lymphocytes were harvested and their concentrations of IL-17 were tested by ELISA. Tumor cells secreted low levels of IL-17 into the media; however, lymphocytes from tumor tissues secreted high levels of IL-17, with 4T1 tumors secreting higher levels of IL-17 than MA782 tumors (P<0.05). To evaluate the effect of IL-17 on the proliferation of tumor cells, 4T1 cells were cultured in the presence or absence of recombinant IL-17 and cell numbers were counted on day 5 of culturing. Ectopic IL-17 did not promote the proliferation of tumor cells in vitro. To further understand the effect of IL-17 expression within tumors, 4T1 tumor-bearing mice were injected with recombinant IL-17 or saline via the tail vein. Tumor size was measured up to 21 days following the initial infusion of IL-17. IL-17 infusion resulted in an increased tumor volume and microvascular density (as measured by the immunohistochemical detection of CD34 expression in microvessels; P<0.05). Therefore, IL-17 expression within tumor tissues appears to originate from tumor-infiltrating lymphocytes and is likely to promote tumor growth by enhancing angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD34 / metabolism
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Female
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Microvessels / metabolism
  • Neovascularization, Pathologic*
  • Phorbol Esters / pharmacology
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD34
  • CD28 Antigens
  • CD3 Complex
  • Interleukin-17
  • Phorbol Esters
  • Recombinant Proteins
  • phorbol-12-myristate