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Role of MT-MMPs and MMP-2 in pancreatic cancer progression

V Ellenrieder1, B Alber, U Lacher

  • 1Department of Internal Medicine, University of Ulm, Ulm, Germany.

International Journal of Cancer
|December 10, 1999
PubMed

Insights

Matrix metalloproteinase-2 (MMP-2) activation by membrane-type MMPs (MT-MMPs) is key in pancreatic cancer. MT1-MMP activates MMP-2, promoting tumor invasion and desmoplasia.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Matrix metalloproteinase-2 (MMP-2) activation by membrane-type MMPs (MT-MMPs) is linked to tumor progression.
  • Pancreatic cancer is characterized by tumor cell invasion and a prominent desmoplastic reaction.

Purpose of the Study:

  • To investigate the roles of MMP-2 and its activators (MT1-MMP, MT2-MMP, MT3-MMP) in pancreatic cancer cell invasion.
  • To determine the association between MMP-2, MT-MMPs, and the desmoplastic reaction in pancreatic cancer tissues.

Main Methods:

  • Northern blot analysis to quantify MT-MMP transcript levels in pancreatic cancer, chronic pancreatitis, and healthy pancreas tissues.
  • Correlation analyses to assess relationships between MT1-MMP, MMP-2 expression/activity, and desmoplastic reaction extent.
  • Invasion assays using pancreatic cancer cell lines, with and without the MMP inhibitor Batimastat.

Main Results:

  • MT1-MMP and MT2-MMP transcript levels were elevated in pancreatic cancer tissues compared to controls.
  • MT1-MMP expression correlated significantly with MMP-2 expression and activity in pancreatic tumors.
  • MMP-2 expression and activity were strongly linked to both tumor cell invasion and the desmoplastic reaction.

Conclusions:

  • MT1-MMP plays a role in pancreatic cancer progression through MMP-2 activation.
  • MMP-2 is crucial for pancreatic tumor cell invasion and is associated with the characteristic desmoplastic reaction.

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