Expression of matrix metalloproteinases (MMPs) during hamster pancreatic duct carcinogenesis and detection of serum MMPs in tumor-bearing hamsters *
The expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and the membrane type of metalloproteinase-1 (MT1-MMP) was investigated in pancreatic ductal carcinomas (PC) induced by N-nitrosobis(2-oxopropyl) amine (BOP), transplantable hamster pancreatic duct carcinoma (HPDt) and pancreatic duct carcinoma ccll lines (HPDc) in hamsters. Northern analysis revealed overexpression of MMP-2, MMP-9, TIMP-2 and MT1-MMP mRNAs in PC and HPDt. Immunohisiochemically, elevated MMP-2 levels were apparent in early duct epithelial hyperplasias and staining increased from atypical hyperplasias to carcinomas. Gelatin zymography demonstrated clear activation of MMP-2 in carcinomas, and proMMP-2 activation correlated with the MT1-MMP mRNA level. Sera from hamsters with HPDt possessed serum MMP-2 levels five times higher than the control sera as determined by gelatin zymographic analysis. These results suggest that overexpression of MMP-2, MMP-9, TIMP-2, and MT1-MMP and activation of proMMP-2 is involved in the progression of pancreatic duct carcinomas and that MMP-2 protein expression appears in the early phase of pancreatic duct carcinogenesis in hamsters. Therefore, serum MMPs may be useful markers for monitoring patients with pancreatic adenocarcinoma. (Accepted on February 23, 1999) Kawasaki Igakkaishi 25(1): 1-10, 1999
