Retinoic Acid Inhibits Pancreatic Cancer Cell Migration and EMT Through the Downregulation of IL-6 in Cancer Associated Fibroblast Cells

Cancer Lett. 2014 Apr 1;345(1):132-9. doi: 10.1016/j.canlet.2013.12.006. Epub 2013 Dec 12.

Abstract

Retinoic acid (RA) is a small molecular derivative of vitamin A that is stored in quiescent stellate cells in pancreas stroma. Cancer associated fibroblasts (CAFs) are activated fibroblast cells in pancreatic ductal adenocarcinoma tumor microenvironment. We treated CAFs with RA and found that these cells became static due to the low expression of α-SMA, FAP, and IL-6 and decreased production of extracellular matrix (ECM). Furthermore, we verified that the low secretion of IL-6 from CAFs was related to RA-induced inhibition of migration and epithelial-mesenchymal transition (EMT) of tumor cells. However, RA could not inhibit the migration and EMT of tumor cells directly. Therefore, our study showed that one of the therapeutic effects of RA on tumor cells is through its modulation of CAFs in tumor microenvironment. The tumor microenvironment plays an important role in promoting tumor migration and might be a promising target of biological treatment.

Keywords: Cancer associated fibroblast cells; EMT; Pancreatic ductal adenocarcinoma; Retinoic acid; Tumor microenvironment; Tumor migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Pancreatic Ductal / drug therapy
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Communication / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / drug effects
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Tretinoin / pharmacology*

Substances

  • Interleukin-6
  • Tretinoin