Cancer-associated fibroblasts’ functional heterogeneity in pancreatic ductal adenocarcinoma

Mohammad Awaji, Rakesh K. Singh

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths in the USA. Desmoplasia and inflammation are two major hallmarks of PDAC. Desmoplasia, composed of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), and infiltrating immune and endothelial cells, acts as a biophysical barrier to hinder chemotherapy and actively contributes to tumor progression and metastasis. CAFs represent a multifunctional subset of PDAC microenvironment and contribute to tumor initiation and progression through ECM deposition and remodeling, as well as the secretion of paracrine factors. Attempts to resolve desmoplasia by targeting CAFs can render an adverse outcome, which is likely due to CAFs heterogeneity. Recent reports describe subsets of CAFs that assume more secretory functions, in addition to the typical myofibroblast phenotype. Here, we review the literature and describe the relationship between CAFs and inflammation and the role of the secretory-CAFs in PDAC.

Original languageEnglish (US)
Article number290
JournalCancers
Volume11
Issue number3
DOIs
StatePublished - Mar 2019

Keywords

  • CXCL8
  • Cancer-associated fibroblast
  • IL-6
  • Inflammation
  • Myofibroblast
  • PDAC
  • Pancreatic cancer
  • TGF-β

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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