Interleukin-6 secreted by oral cancer- associated fibroblast accelerated VEGF expression in tumor and stroma cells

Cell Mol Biol (Noisy-le-grand). 2017 Oct 31;63(10):131-136. doi: 10.14715/cmb/2017.63.10.21.

Abstract

Oral cancer represents the sixth most common cancer type worldwide. Patients with oral cancer express high levels of IL-6 which is associated with very poor prognosis. Previous studies illustrated that IL-6 cytokine induces angiogenesis. It has also been reported that the presence of Cancer- Associated Fibroblasts (CAFs) is essential for angiogenesis. In this study, we examined the correlation between IL-6 and CAF and the role of this correlation on VEGF production. In this study, quantitative expression level of IL-6 and VEGF in CAF and Oral Cancer Cells (OCCs) examined through Real Time PCR and ELISA and western blot analysis. In addition, maintenance and retention of IL-6 and VEGF checked out in co-culture experiment of CAF and OCC cells. These experiments demonstrated that in oral cancer, CAF cell line secretes significantly more IL-6 than OCC. Also IL-6 is a factor that causes VEGF secretion in CAF cell line. CAF is the basic and the most essential source for producing IL-6 in patients with oral cancer. Secreted IL-6 is able to induce VEGF production in both CAF and OCCs. Correlation between CAF, IL-6 and VEGF could be considered as an approach for cancer therapy.

Keywords: Cancer- Associated fibroblast; Interleukin-6; Normal fibroblast.; Oral cancer cells; VEGF.

MeSH terms

  • Actins / metabolism
  • Coculture Techniques
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-6 / analysis*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / toxicity
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Real-Time Polymerase Chain Reaction
  • Stromal Cells / cytology
  • Stromal Cells / metabolism
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / analysis*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vimentin / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Interleukin-6
  • Lipopolysaccharides
  • Vascular Endothelial Growth Factor A
  • Vimentin