Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice

Cancer Res. 1999 Aug 1;59(15):3698-704.

Abstract

Interleukin (IL) 17 is a proinflammatory cytokine secreted mainly by activated human memory CD4 T cells that induces IL-6, IL-8, and nitric oxide. Because IL-6 and IL-8 have been implicated in the pathogenesis of cervical cancer, we investigated the action of IL-17 on human cervical tumor cell lines in vitro and in vivo. We showed that in vitro, IL-17 increases IL-6 and IL-8 secretion by cervical carcinoma cell lines at both protein and mRNA levels. No direct effect of IL-17 on in vitro proliferation of cervical tumor cell lines could be demonstrated. However, two cervical cell lines transfected with a cDNA encoding IL-17 exhibited a significant increase in tumor size as compared to the parent tumor when transplanted in nude mice. This enhanced tumor growth elicited by IL-17 was associated with increased expression of IL-6 and macrophage recruitment at the tumor site. A potential role of IL-17 in modulation of the human cervical tumor phenotype was also supported by its expression on the cervical tumor in patients with CD4 infiltration. IL-17 therefore behaves like a T-cell-specific cytokine with paradoxical tumor-promoting activity. This may partially explain previous reports concerning the deleterious effect of CD4 T cells in cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / pathology
  • Carcinogens / toxicity*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • HeLa Cells / drug effects
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / toxicity*
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Male
  • Melanoma / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Transplantation
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / toxicity
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / metabolism*
  • Transfection
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / transplantation
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Carcinogens
  • Interleukin-17
  • Interleukin-6
  • Interleukin-8
  • Neoplasm Proteins
  • Recombinant Fusion Proteins