Abstract
Esophageal adenocarcinoma (EAC) has become the dominant type of esophageal cancer in United States. The 5-year survival rate of EAC is below 20% and most patients present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Improvement of EAC patient 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 EAC that would support survival outcome analyses. To find the best candidate cell line from 7 human EAC cell lines of different origin named ESO26, OE33, ESO51, SK-GT-2, OE19, OACM5.1C and Flo-1 were injected intraperitoneally/subcutaneously into SCID mice. The peritoneal/xenograft tumor formation and mouse survival were compared among different groups. 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 = 0.00011). Thus peritoneal dissemination mouse xenograft model for survival outcome assessment after intraperitoneal injection of OE19 cells will be very useful for the evaluation of cancer therapeutics.
Highlights
Esophageal adenocarcinoma (EAC) has become the dominant type of esophageal cancer in United States
We present for the first time the successful establishment of a peritoneal dissemination mouse xenograft model for survival outcome analysis with intraperitoneal injection of human EAC cell lines
After intraperitoneal injection of 5X106 EAC cells in SCID mice earliest multiple peritoneal tumor formation was observed in the OE19 model, followed by the OE33 and the SK-GT-2 models (Fig 1B, 1C and 1D)
Summary
Esophageal adenocarcinoma (EAC) has become the dominant type of esophageal cancer in United States. EAC represents the fastest growing cancer in the western world. The incidence of EAC is increasing while the incidence of esophageal squamous cell remains unchanged [1,2,3,4,5,6]. Despite recent advances in surgical and radiation technique as well as in systemic medical treatment, prognosis of EAC remains poor [7,8,9]. The overall 5 year survival rate of EAC is below 20% and most patients present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective [10, 11]. The poor survival rate of EAC patients warrants further evaluation of other anticancer drugs that block potential pathways of EAC progression
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