Pancreatic cancer and its stroma: a conspiracy theory

World J Gastroenterol. 2014 Aug 28;20(32):11216-29. doi: 10.3748/wjg.v20.i32.11216.

Abstract

Pancreatic cancer is characterised by a prominent desmoplastic/stromal reaction that has received little attention until recent times. Given that treatments focusing on pancreatic cancer cells alone have failed to significantly improve patient outcome over many decades, research efforts have now moved to understanding the pathophysiology of the stromal reaction and its role in cancer progression. In this regard, our Group was the first to identify the cells (pancreatic stellate cells, PSCs) that produced the collagenous stroma of pancreatic cancer and to demonstrate that these cells interacted closely with cancer cells to facilitate local tumour growth and distant metastasis. Evidence is accumulating to indicate that stromal PSCs may also mediate angiogenesis, immune evasion and the well known resistance of pancreatic cancer to chemotherapy and radiotherapy. This review will summarise current knowledge regarding the critical role of pancreatic stellate cells and the stroma in pancreatic cancer biology and the therapeutic approaches being developed to target the stroma in a bid to improve the outcome of this devastating disease.

Keywords: Metastasis; Pancreatic cancer; Pancreatic stellate cells; Stromal reaction; Tumour-stroma interactions.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Cell Communication*
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Extracellular Matrix / metabolism
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Neovascularization, Pathologic
  • Pancreatic Neoplasms / blood supply
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / therapy
  • Pancreatic Stellate Cells / immunology
  • Pancreatic Stellate Cells / metabolism
  • Pancreatic Stellate Cells / pathology*
  • Prognosis
  • Signal Transduction
  • Stromal Cells / immunology
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*
  • Tumor Escape
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor