A protective role by interleukin-17F in colon tumorigenesis

PLoS One. 2012;7(4):e34959. doi: 10.1371/journal.pone.0034959. Epub 2012 Apr 11.


Interleukin-17F (IL-17F), produced by Th17 cells and other immune cells, is a member of IL-17 cytokine family with highest homology to IL-17A. IL-17F has been shown to have multiple functions in inflammatory responses. While IL-17A plays important roles in cancer development, the function of IL-17F in tumorigenesis has not yet been elucidated. In the current study, we found that IL-17F is expressed in normal human colonic epithelial cells, but this expression is greatly decreased in colon cancer tissues. To examine the roles of IL-17F in colon cancer, we have used IL-17F over-expressing colon cancer cell lines and IL-17F-deficient mice. Our data showed decreased tumor growth of IL-17F-transfected HCT116 cells comparing to mock transfectants when transplanted in nude mice. Conversely, there were increased colonic tumor numbers and tumor areas in Il-17f(-/-) mice than those from wild-type controls after colon cancer induction. These results indicate that IL-17F plays an inhibitory role in colon tumorigenesis in vivo. In IL-17F over-expressing tumors, there was no significant change in leukocyte infiltration; instead, we found decreased VEGF levels and CD31(+) cells. While the VEGF levels were increased in the colon tissues of Il-17f(-/-) mice with colon cancer. Together, our findings demonstrate a protective role for IL-17F in colon cancer development, possibly via inhibiting tumor angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism*
  • Epithelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Interleukin-17 / genetics*
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / immunology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism


  • Interleukin-17
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A