Abstract A75: Overexpression of Wnt1 induces ovarian-type stroma that resemble human pancreatic mucinous cystic neoplasm (MCN).

Abstract

Pancreatic mucinous cystic neoplasm (MCN), a cystic tumor of the pancreas with a predominant female gender bias, occurs primarily in the body and tail of the pancreas and is characterized by the presence of a mucinous epithelium and ovarian-type stroma. To determine the involvement of Wnt ligand-induced signaling in pancreatic tumorigenesis, we combined the established LSL-KrasG12D, Ptf1a-cre model with the elastase-tva transgenic mouse to facilitate the delivery of avian leukosis virus-based RCASWnt1 viruses to the pancreatic epithelium. We found that female mice injected with RCAS-Wnt1, but not RCAS-GFP, commonly developed unilocular or multilocular cysts, sometimes including hemorrhagic contents (so called chocolate cyst), in the pancreas body and tail. The cystic lesions were composed of the characteristic ovarian-type stroma that was positive for estrogen receptor (ER) and progesterone receptor (PR) expression; however, they lacked the typical mucinous epithelium. Interestingly, activation of Wnt/β-catenin and PCP signaling pathways – as determined by nuclear β-catenin, p-JNK and p-Rock2 positivity – was detected in the stroma, but not the cyst epithelium. Analysis of human MCN cases identified activation of both the Wnt/β-catenin and PCP signaling pathways in the ovarian-type stroma, but not the cyst epithelium, consistent with our findings in the mouse model. Together, these data suggest that activation of the canonical and non-canonical Wnt signaling pathways stimulates the development of the ovarian-type stroma observed in pancreatic MCN and contributes to MCN formation in vivo. Citation Format: Makoto Sano, David Driscoll, David S. Klimstra, Wilfredo DeJesus-Monge, Victoria Appleman, Brian Quattrochi, Brian C. Lewis. Overexpression of Wnt1 induces ovarian-type stroma that resemble human pancreatic mucinous cystic neoplasm (MCN). [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A75.