Cancer Associated Fibroblasts Derived from Pancreatic Adenocarcinoma and Their Role in Cell Migration

Anticancer Res. 2021 Sep;41(9):4229-4238. doi: 10.21873/anticanres.15227. Epub 2021 Sep 1.

Abstract

Background/aim: Pancreatic ductal adenocarcinoma (PDAC) shows poor survival and early systemic dissemination. Cancer associated fibroblasts (CAFs) enhance migration and invasion of cancer cells. We aimed to investigate the role of CAFs in cell migration and their underlying paracrine effects.

Materials and methods: Using Transwell® migration assays, PDAC cells (PANC-1) and three distinct types of fibroblasts were analyzed: CAFs, genetically transformed human foreskin-fibroblasts (BJeLR), and non-transformed human foreskin-fibroblasts (VH7). IL6 in the culture supernatant was measured to investigate paracrine communication in monocultures and direct/indirect cocultures.

Results: CAFs showed a significantly higher capacity to migrate in vitro when compared to benign fibroblasts (p=0.009). They also facilitated the migration of PDAC cells in coculture (p=0.001). Neither BJeLR, nor VH7 displayed such features. This was accompanied by a significant increase in IL-6 when CAFs were cocultured with PANC-1 (p=0.009).

Conclusion: CAFs are a key element of intra-tumoral migration and should be further investigated as a potential therapeutic target.

Keywords: Pancreatic cancer; cancer associated fibroblasts; migration; paracrine communication..

Publication types

  • Comparative Study

MeSH terms

  • Cancer-Associated Fibroblasts / cytology*
  • Cancer-Associated Fibroblasts / immunology
  • Cancer-Associated Fibroblasts / pathology
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Female
  • Foreskin / cytology*
  • Foreskin / immunology
  • Humans
  • Interleukin-6 / metabolism*
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology*
  • Paracrine Communication
  • Tumor Microenvironment

Substances

  • IL6 protein, human
  • Interleukin-6