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

Activation of matrix metalloproteinase-2 (MMP-2) by the membrane-type matri x metalloproteinases (MT-MMPs) has been associated with tumor progression. In the present study, we examined the role of MMP-2 and its activators MTI- MMP, MT2-MMP and MT3-MMP in pancreatic tumor cell invasion and the developm ent of the desmoplastic reaction characteristic of pancreatic cancer tissue s. Northern blot analyses revealed that transcript levels of MTI-MMP and MT 2-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 MTI-MMP and both MMP-2 expression (p < 0.01) and activity in pancreatic cancer tissues. In addition, express ion 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 o f MMP-2 expression and activity, the MMP inhibitor Batimastat led to signif icant reduction of the number of invading cells. Our results suggest that M TI-MMP is involved in the progression of pancreatic cancer via activation o f MMP-2. MMP-2 itself plays an important role in tumor cell invasion and ap pears to be associated with the development of the characteristic desmoplas tic reaction in pancreatic cancer. (C) 2000 Wiley-Liss, Inc.