Abstract 4173: In vivo and in vitro propagation of Intraductal Papillay Mucinous Neoplasms

Background Intraductal Papillary Mucinous Neoplasms (IPMNs) are one of the 3 known curable precursor lesions (IPMN, MCN (Mucinous Cystic Neoplasm), and PanIN (Pancreatic Intraepithelial Neoplasm)) of invasive pancreatic ductal adenocarcinoma, an almost uniformly fatal disease. Methods To advance the study of the biological features of IPMNs, we attempted in vivo and in vitro growth of selected IPMNs, based on the hypothesis that IPMNs could be grown in the most severely immunodeficient mice. We examined fourteen cases by implanting them into nude, severe combined immunodeficient (SCID), and NOD/SCID/IL2Rγ null (NOG) mice, in addition to direct culture, to generate tumor xenografts and cell lines. Results Thirteen tumors were implanted into the 3 types of mice, including 10 tumors implanted into the triple immunodeficient NOG mice, where the majority (8 of 10) grew including 5 IPMNs lacking invasive components. One of the explanted IPMNs, with an associated invasive carcinoma, was successfully established as a cell line. Growth in soft agar, growth in mice and homozygous deletion of P16/cdkn2a confirmed its tumorigenicity. The expression of cytokeratin confirmed the epithelial differentiation of the cell line, and DNA fingerprinting confirmed its human origin. Future directions Isolating cell lines from IPMNs and their invasion counterparts should be valuable to identify gene mutations critical to IPMN carcinogenesis, and permit drug screening to identify compounds that cause regression of those lesions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4173.