Abstract 1502: DCLK1 labeling a unique pancreatic cellular lineage contributes to intraductal papillary mucinous neoplasm development

Abstract BACKGROUND & AIMS: Recently DCLK1 has been controversial as a biomarker of progenitor cells in both intestinal tract and pancreas. Pancreatic intraductal papillary mucinous neoplasm (IPMN), in contrast to pancreatic intraepithelial neoplasia (PanIN), has been relatively less investigated. Here, we explored whether DCLK1-expressing cells were involved in the genesis of pancreatic IPMNs using mouse models. METHODS: We compared the incidence of DCLK1-positive cells in pancreatic tissue samples derived from mouse models for IPMNs, PanINs, acinar to ductal metaplasia (ADM), and human IPMN samples by immunohistochemistry. And how the DCLK1+ cells engage ADM and IPMNs and its origin were investigated by in vitro culture and in vivo lineage tracing. RESULTS: The DCLK1+ cells were identified exclusively in the pancreatic tissues with activated oncogene compared to wild-type. Mouse lineage tracing experiments showed that DCLK1+ cells might originate from a cell lineage distinct from pancreatic PDX1 (+) progenitors. The pancreatic DCLK1+ cells shared the features of tuft cells but absence of IPMN tumor biomarkers. DCLK1+ cells presented in the acinar clusters prior to formation of metaplastic ductal cells, and enriched in the “IPMN niches”. Oncogenic signaling pathways such as SHH and DLL4 were activated or upregulated in the tumor cells but not the DCLK1+ cells of IPMNs. DCLK1 was also expressed in a subpopulation of tumor cells in 20% of human IPMN patients. CONCLUSIONS: DCLK1 labels a unique pancreatic cellular lineage in mouse. The clustering of DCLK1+ cells is an early event in oncogene-induced tumorigenesis. Pancreatic DCLK1+ cells may contribute to the initiation of ADM and its progression to IPMNs. Key words: Pancreatic IPMN; ADM; DCLK1; SOX9. Citation Format: Wanglong Qiu, Gloria Su. DCLK1 labeling a unique pancreatic cellular lineage contributes to intraductal papillary mucinous neoplasm development. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1502. doi:10.1158/1538-7445.AM2015-1502