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

✍ Scribed by Volker Ellenrieder; Burkhard Alber; Ulrike Lacher; Sandra F. Hendler; Andre Menke; Wolfgang Boeck; Martin Wagner; Monika Wilda; Helmut Friess; Markus Büchler; Guido Adler; Thomas M. Gress

Publisher
John Wiley and Sons
Year
2000
Tongue
French
Weight
277 KB
Volume
85
Category
Article
ISSN
0020-7136

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✦ Synopsis

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 F 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.

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