Introduction: Esophageal adenocarcinoma (EAC) has become the dominant type of esophageal cancer in United States. EAC is the fastest growing cancer in the western world and the overall 5 year survival rate of EAC is below 20 percent. Most patients present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Prognosis for EAC patients remains poor even with combination therapies due to high resistance to chemotherapy. Therefore, new therapeutic approaches are urgently needed. Improvement of esophageal adenocarcinoma outcome requires well-characterized animal models in which to evaluate novel therapeutics. In this study we aimed to establish a peritoneal dissemination xenograft mouse model of esophageal adenocarcinoma that would support survival outcome analyses.

Methods: To find the best candidate cell line from 7 esophageal adenocarcinoma cell lines of various origin, we injected them intraperitoneally and subcutaneously into severe combined immunodeficiency (SCID) mice and examined the tumor progression and survival outcomes. Human esophageal adenocarcinoma cell lines of Caucasian/Hispanic origin ESO26, OE33, ESO51, SK-GT-2, OE19, OACM5.1C and Flo-1 originating from gastroesophageal junction, distal esophagus and gastric cardia/fundus were injected intraperitoneally/subcutaneously into SCID mice. The peritoneal/xenograft tumor formation and mouse survival were compared among different groups.

Results: All cell lines injected subcutaneously formed tumors within 3 months at variable rates. All cell lines except OACM5.1C formed intraperitoneal tumors within 3 months at variable rates. Median animal survival with peritoneal dissemination was 108 days for ESO26 cells (5X106), 65 days for OE33 cells (5X106), 88 days for ESO51 cells (5X106), 76 days for SK-GT-2 cells (5X106), 55 days for OE19 cells (5X106), 45 days for OE19 cells (10X106) and 82 days for Flo-1 cells (5X106). Interestingly, only in the OE19 model all mice (7/7 for 5X106 and 5/5 for10X106) developed bloody ascites with liver metastasis after intraperitoneal injection. The median survival time of these animals was the shortest (45 days for 10X106 cells). In addition, median survival was significantly increased after paclitaxel treatment compared with the control group (57 days versus 45 days, p=0.0034) along with a significant decrease of the relative subcutaneous tumor volume (p=0.023).

Conclusion: Peritoneal esophageal adenocarcinoma xenografts were successfully established after intraperitoneal injection of OE19 cells. This animal model of peritoneal dissemination for survival outcome will provide a useful survival outcome assessment model for the preclinical evaluation of cancer therapeutics in esophageal adenocarcinoma.

Citation Format: Md Sazzad Hassan, Niranjan Awasthi, Roderich E. Schwarz, Margaret A. Schwarz, Urs von Holzen. A novel intraperitoneal metastatic xenograft mouse model for survival outcome assessment of esophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2826. doi:10.1158/1538-7445.AM2017-2826