Role of MT-MMPs and MMP-2 in Pancreatic Cancer Progression

Int J Cancer. 2000 Jan 1;85(1):14-20. doi: 10.1002/(sici)1097-0215(20000101)85:1<14::aid-ijc3>3.0.co;2-o.

Abstract

Activation of matrix metalloproteinase-2 (MMP-2) by the membrane-type matrix metalloproteinases (MT-MMPs) has been associated with tumor progression. In the present study, we examined the role of MMP-2 and its activators MT1-MMP, MT2-MMP and MT3-MMP in pancreatic tumor cell invasion and the development of the desmoplastic reaction characteristic of pancreatic cancer tissues. Northern blot analyses revealed that transcript levels of MT1-MMP and MT2-MMP, but not MT3-MMP, were enhanced in pancreatic cancer tissues (n = 18) compared with both chronic pancreatitis (n = 9) and healthy pancreas (n = 9). A good correlation was found between MT1-MMP and both MMP-2 expression (p < 0.01) and activity in pancreatic cancer tissues. In addition, expression and activation of MMP-2 were strongly associated with the extent of the desmoplastic reaction in pancreatic cancer tissues. Invasion assays showed a good correlation between MMP-2 expression and activity and the invasive potential of pancreatic cancer cell lines. In cell lines with high levels of MMP-2 expression and activity, the MMP inhibitor Batimastat led to significant reduction of the number of invading cells. Our results suggest that MT1-MMP is involved in the progression of pancreatic cancer via activation of MMP-2. MMP-2 itself plays an important role in tumor cell invasion and appears to be associated with the development of the characteristic desmoplastic reaction in pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / pathology
  • Disease Progression
  • Fibrosis / pathology
  • Gelatin / metabolism
  • Humans
  • Matrix Metalloproteinase 15
  • Matrix Metalloproteinase 16
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 2 / physiology*
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / biosynthesis*
  • Matrix Metalloproteinases / metabolism
  • Matrix Metalloproteinases / physiology*
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases*
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • Tumor Cells, Cultured

Substances

  • MMP15 protein, human
  • MMP16 protein, human
  • RNA, Messenger
  • Gelatin
  • Matrix Metalloproteinase 15
  • Matrix Metalloproteinase 16
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9