Oxidative stress induced autophagy in cancer associated fibroblast enhances proliferation and metabolism of colorectal cancer cells

Cell Cycle. 2017 Jan 2;16(1):73-81. doi: 10.1080/15384101.2016.1252882. Epub 2016 Nov 14.

Abstract

Tumors are comprised of malignant cancer cells and stromal cells which constitute the tumor microenvironment (TME). Previous studies have shown that cancer associated fibroblast (CAF) in TME is an important promoter of tumor initiation and progression. However, the underlying molecular mechanisms by which CAFs influence the growth of colorectal cancer cells (CRCs) have not been clearly elucidated. In this study, by using a non-contact co-culture system between human colorectal fibroblasts (CCD-18-co) and CRCs (LoVo, SW480, and SW620), we found that fibroblasts existing in tumor microenvironment positively influenced the metabolism of colorectal cancer cells, through its autophagy and oxidative stress pathway which were initially induced by neighboring tumor cells. Therefore, our data provided a novel possibility to develop fibroblasts as a potential target to treat CRC.

Keywords: 3-MA; Colorectal cancer; NAC; autophagy; co-culture; metabolism; oxidative stress.

MeSH terms

  • Acetylcysteine / pharmacology
  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Autophagy* / drug effects
  • Blotting, Western
  • Cancer-Associated Fibroblasts / metabolism*
  • Cancer-Associated Fibroblasts / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coculture Techniques
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Humans
  • Oxidative Stress* / drug effects

Substances

  • 3-methyladenine
  • Adenine
  • Acetylcysteine