IL-17 Is Associated With Poor Prognosis and Promotes Angiogenesis via Stimulating VEGF Production of Cancer Cells in Colorectal Carcinoma

Biochem Biophys Res Commun. 2011 Apr 8;407(2):348-54. doi: 10.1016/j.bbrc.2011.03.021. Epub 2011 Mar 9.

Abstract

IL-17, which exerts strong pro-inflammatory effects, has emerged as an important mediator in inflammation-associated cancer. However, the characteristics of IL-17-producing cells, the relevance of IL-17 to clinical parameters and its function in the development and progression of colorectal carcinoma still remain to be explored. In the present study, we first found the levels of IL-17 producing cells were significantly increased in the tumor regions of samples from colorectal carcinoma patients compared with non-tumor regions. Confocal microscopic analysis showed co-staining of IL-17 with CD4 and CD68, indicating IL-17 in colorectal carcinoma was expressed by macrophage and Th17. High expression of IL-17 was associated with high microvessel density. Univariate and multivariate analysis revealed that IL-17 was an independent prognostic factor for overall survival. To explore the underlying mechanisms of IL-17 in angiogenesis, we used PCR-array to find pro-angiogenic factor in cancer cells specifically induced by IL-17, then validated VEGF as one of factors in IL-17-mediated angiogenesis with the use of quantitative RT-PCR, ELISA and VEGF immunohistochemistry. Our results propose IL-17 as a novel indicator of prognosis in the patients with colorectal carcinoma and could serve as a novel therapeutic target for colorectal carcinoma, furthermore our results indicate that IL-17 producing cells may facilitate development of colorectal carcinoma by fostering angiogenesis via promote VEGF production from cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • CD5 Antigens / metabolism
  • Carcinoma / blood supply*
  • Carcinoma / metabolism*
  • Carcinoma / pathology*
  • Colorectal Neoplasms / blood supply*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Humans
  • Interleukin-17 / metabolism*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic
  • Prognosis
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD5 Antigens
  • CD68 antigen, human
  • Interleukin-17
  • Vascular Endothelial Growth Factor A