MT1-MMP cooperates with Kras(G12D) to promote pancreatic fibrosis through increased TGF-β signaling.

ABSTRACT: Pancreatic cancer is associated with a pronounced fibrotic reaction that was recently shown to limit delivery of chemotherapy. To identify potential therapeutic targets to overcome this fibrosis, we examined the interplay between fibrosis and the key proteinase membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14), which is required for growth and invasion in the collagen-rich microenvironment. In this article, we show that compared with control mice (Kras(+)/MT1-MMP(-)) that express an activating Kras(G12D) mutation necessary for pancreatic cancer development, littermate mice that express both MT1-MMP and Kras(G12D) (Kras(+)/MT1-MMP(+)) developed a greater number of large, dysplastic mucin-containing papillary lesions. These lesions were associated with a significant amount of surrou

SUBMITTER: Krantz SB 

PROVIDER: S-EPMC3196812 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature