Abstract 1710: Novel syngeneic mouse gastric cancer models identified Sca-1 as a gastric cancer stem cell marker

Abstract

Abstract Genetically well-defined syngeneic mouse models for gastric cancer are not available in the scientific community, but critical for the development of immunotherapeutic agents. We generated primary mouse gastric cancer cell line NCC-S1 (S1) established from a Villin-cre;Smad4F/F;Trp53F/F;Cdh1F/wt mouse and its metastatic variant cell line NCC-S1M (S1M). These cells closely recapitulated human diffuse type gastric cancers in histology and molecular profiles. S1M cells showed enhanced in vivo growth and metastatic potentials compared with S1 cells, and developed orthotopic and heterotopic tumors in immunocompetent mice in predictable manner. S1M allograft model was useful for testing the efficacy of an immunotherapeutic agent, anti-4-1BB. Sca-1 was overexpressed in S1M cells compared with S1 cells. Approximately 7% of gastric cancer cells in primary tumors expressed Sca-1. Sca-1high cells were more tumorigenic according to the in vivo limiting dilution assay, and more resistant to cisplatin and fluorouracil. Sca-1high cells overexpressed CD133, CD44, EPCAM and Bcl-xL. A chromatin immunoprecipitation analysis demonstrated that Sca-1 was a β-catenin/LEF1 target gene. Expression profiles of 85 genes overexpressed in Sca-1high S1 cells clustered 123 pretreatment gastric cancer patient samples according to the overall survival following cisplatin/fluorouracil chemotherapy. Thus, our novel metastatic gastric cancer cell lines are useful resources for drug development, and identified Sca-1 as a novel gastric cancer stem cell marker that mediates β-catenin signaling. Citation Format: Jun Won Park, Hark K. Kim. Novel syngeneic mouse gastric cancer models identified Sca-1 as a gastric cancer stem cell marker. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1710.