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Role of MT‐MMPs and MMP‐2 in pancreatic cancer progression
Author(s) -
Ellenrieder Volker,
Alber Burkhard,
Lacher Ulrike,
Hendler Sandra F.,
Menke Andre,
Boeck Wolfgang,
Wagner Martin,
Wilda Monika,
Friess Helmut,
Büchler Markus,
Adler Guido,
Gress Thomas M.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000101)85:1<14::aid-ijc3>3.0.co;2-o
Subject(s) - matrix metalloproteinase , pancreatic cancer , pancreas , cancer research , cancer , biology , tumor progression , pathology , pancreatitis , pancreatic disease , cancer cell , medicine , endocrinology
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. Int. J. Cancer 85:14–20, 2000. © 2000 Wiley‐Liss, Inc.