Development and Biological Analysis of a Novel Orthotopic Peritoneal Dissemination Mouse Model Generated Using a Pancreatic Ductal Adenocarcinoma Cell Line.

Abstract

Peritoneal dissemination (PD) is an important cause of morbidity and mortality among patients with pancreatic ductal adenocarcinoma (PDAC). We sought to develop and characterized a novel PD mouse model by using a previously established PDAC cell line TCC-Pan2. TCC-Pan2 cell line was characterized for growth rate, tumor markers, histology, and somatic mutations. TCC-Pan2 cells were implanted orthotopically to produce PD. TCC-Pan2 cells from these metastatic foci were expanded in vitro and then implanted orthotopically in mice. This PD model was used for comparing the antitumor effect of paclitaxel and NK105. Orthotopically implanted TCC-Pan2 cells caused tumor formation and PD with high frequency in mice. A potent metastatic subline-Pan2M-was obtained. NK105 exerted a stronger antitumor effect than paclitaxel against Pan2M cells harboring a luciferase gene (Pan2MmLuc). Notably, the survival rate on day 80 in the Pan2MmLuc mouse model was 100% for the NK105 group and 0% for the paclitaxel group. TCC-Pan2 cell line and Pan2MmLuc PD model can serve as useful tools for monitoring the responses to antineoplastic agents and for studying PDAC biology.