Cancer-associated fibroblasts in pancreatic adenocarcinoma

Future Oncol. 2015 Sep;11(18):2603-10. doi: 10.2217/FON.15.176. Epub 2015 Aug 18.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most highly malignant tumors with a very poor prognosis. In addition to the cancer cells, the stroma of tumor can expand by 50% and influence cancer cell growth. Cancer-associated fibroblasts (CAFs) are important components of tumor stroma. Cancer cells, normal fibroblasts, normal epithelial cells as well as bone marrow-derived myofibroblasts contribute to the emergence of CAFs through various cytokines (e.g., TGF-β, SHH, PDGF) and epithelial-to-mesenchymal transition. CAFs affect cancer growth, survival, metastasis, angiogenesis and immunosurveillance through the secretion of various cytokines, such as CXCL12 and secreted protein acidic and rich in cystein. Also, CAFs correlate to the prognosis and chemoresistance of PDAC patients. As novel therapeutic targets, CAFs, and their relative factors, represent an important role in PDAC therapy.

Keywords: CAFs; CXCL12; SPARC; chemotherapy; pancreatic ductal adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Pancreatic Ductal / drug therapy
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Proliferation
  • Cell Survival
  • Drug Resistance, Neoplasm
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neovascularization, Pathologic
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Prognosis

Substances

  • Antineoplastic Agents