Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas
Howard C. Crawford, … , Lynn M. Matrisian, Steven D. Leach
Howard C. Crawford, … , Lynn M. Matrisian, Steven D. Leach
Published June 1, 2002
Citation Information: J Clin Invest. 2002;109(11):1437-1444. https://doi.org/10.1172/JCI15051.
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Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas

Abstract

In gastrointestinal epithelium, metaplastic conversion between predominant cell types is associated with an increased risk of neoplasia. However, the mechanisms regulating metaplastic transitions in adult epithelia are largely undefined. Here we show that matrix metalloproteinase-7 (MMP-7) is expressed not only in the majority of human pancreatic ductal adenocarcinoma specimens, but also in human pancreatic intraepithelial neoplasia and metaplastic duct lesions in human and mouse. In a mouse model of pancreatic acinar-to-ductal metaplasia, MMP-7 progressively accumulates during the metaplastic transition, resulting in a concomitant increase in solubilization of Fas ligand (FasL). Under identical conditions, mice either deficient in MMP-7 or carrying an inactive FasL gene are severely inhibited in development of progressive metaplasia and acinar cell apoptosis. Thus, MMP-7 and FasL influence the initiation and maintenance of metaplastic events in pancreatic epithelium, explaining the observed link between metaplasia and apoptosis in pancreas and other gastrointestinal tissues.

Authors

Howard C. Crawford, Charles R. Scoggins, M. Kay Washington, Lynn M. Matrisian, Steven D. Leach

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MMP-7 expression in PDACs, PanINs, and metaplastic ducts. MMP-7 immunore...
MMP-7 expression in PDACs, PanINs, and metaplastic ducts. MMP-7 immunoreactivity in (a) normal pancreas (scale bar, 140 μm); (b) well-differentiated invasive adenocarcinoma (scale bar, 70 μm); (c) PanIN-1 (scale bar, 55 μm); (d) PanIN-2 (scale bar, 55 μm); (e) PanIn-3 (scale bar, 100 μm); (f) both PanIN-3 (arrowhead) and surrounding metaplastic duct lesions (arrows; scale bar, 100 μm); (g and h) metaplastic epithelium of CP specimen. Asterisks are used to show point of reference between g and h (scale bars represent 140 μm and 36 μm, respectively).