Abstract 1336: Concurrent Snail expression and Kras mutation promote pancreatic fibrosis

Abstract One of the hallmarks of pancreatic ductal adenocarcinoma (PDAC), the 4th leading cause of cancer related death in the US, is a pronounced collagen-rich stromal reaction. We recently published that type I collagen induces expression of Snail, a key regulator of epithelial-mesenchymal transition, to promote invasion and scattering of PDAC cells (Shields MA, et al. JBC 2011). To further understand the role of Snail in PDAC progression we generated transgenic mice expressing Snail in the pancreas. While there was robust Snail expression in the mouse pancreas, no phenotypic changes were observed. Since inflammation can promote Snail-mediated invasion and metastasis, we treated the Snail-expressing mice with cerulein to induce chronic pancreatitis. Although there was significant inflammation associated with vacuolization, no difference in the pancreatitis response was observed between control and Snail-expressing mice. Since Kras mutation has been shown to be necessary for tumor development in mouse models of pancreatic cancer, we generated mice expressing both mutant KrasG12D and Snail (Kras+/Snail+). Compared to control mice (Kras+/Snail-), Kras+/Snail+ mice developed significantly more acinar to ductal metaplasia, cystic papillary lesions that were associated with increased fibrosis, increased Smad2 and Stat3 phosphorylation. Experiments are underway characterizing the mechanism by which Snail promotes pancreatic fibrosis in Kras-expressing mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1336. doi:1538-7445.AM2012-1336