Biochemical role of the collagen-rich tumour microenvironment in pancreatic cancer progression

Mario A. Shields, Surabhi Dangi-Garimella*, Amanda J. Redig, Hidayatullah G. Munshi

*Corresponding author for this work

Research output: Contribution to journalReview article

116 Scopus citations

Abstract

PDAC (pancreatic ductal adenocarcinoma) is among the most deadly of human malignances. A hallmark of the disease is a pronounced collagen-rich fibrotic extracellular matrix known as the desmoplastic reaction. Intriguingly, it is precisely these areas of fibrosis in which human PDAC tumours demonstrate increased expression of a key collagenase, MT1-MMP [membrane-type 1 MMP (matrix metalloproteinase); also known as MMP-14]. Furthermore, a cytokine known to mediate fibrosis in vivo, TGF- β1 (transforming growth factor-β1), is up-regulated in human PDAC tumours and can promote MT1-MMP expression. In the present review, we examine the regulation of PDAC progression through the interplay between type I collagen (the most common extracellular matrix present in human PDAC tumours), MT1- MMP and TGF-β1. Specifically, we examine the way in which signalling events through these pathways mediates invasion, regulates microRNAs and contributes to chemoresistance.

Original languageEnglish (US)
Pages (from-to)541-552
Number of pages12
JournalBiochemical Journal
Volume441
Issue number2
DOIs
StatePublished - Jan 15 2012

Keywords

  • Chemoresistance
  • Fibrosis
  • Membrane-type 1 matrix metalloproteinase (MT1-MMP)
  • MicroRNA
  • Pancreatic cancer
  • Snail
  • Transforming growth factor-β (TGF-β)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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