Abstract 5112: Interaction between RHOA mutated gastric cancer cells and cancer associated fibroblasts promotes tumorigenesis

Abstract

Abstract Background: We previously observed that RHOA-mutated gastric cancer has desmoplastic morphological feature. Although desmoplastic reaction is known to consist mainly of cancer associated fibroblasts (CAF), the relationship cancer cells with RHOA mutation and CAF have not been reported. Thus, in this study, we investigated the interaction between RHOA-mutated gastric cancer cells and CAF and its underlying mechanism. Methods: We established stable gastric cell lines (AGS, MKN-45) expressing RHOA wild type (WT) of mutation (G17E, T37I, E40K, Y42C) using lentiviral vector and cocultured these cells with CAF using transwell. And proliferation and migration of RHOA-mutated gastric cancer cells were examined. To understand molecular mechanism of RHOA-mutated gastric cancer cells proliferation and migration, RNA-sequencing was conducted and the results were analyzed and validated. Results: Cocultivation of gastric cancer cells expressing RHOA WT or mutation (G17E, T37I, E40K, Y42C) with CAF increased proliferation relative to cells expressing an empty vector (EV). In addition, migration of RHOA mutant cells, except for cells with RHOA WT and Y42C, was increased by CAF relative to EV cells. Genes related to IL-17, IL-15, and IGF-1 signaling pathways were differentially expressed between RHOA WT or mutant cells and EV cells, suggesting that proliferation and migration of RHOA mutant cells promoted by CAF through these pathways. Furthermore, we identified CXCL1 and IGFBP2 as mediator of interaction between RHOA mutated gastric cancer cells and CAF. Conclusion: In summary, we found that gastric cancer cells with RHOA mutation have tumor-promoting activity by interaction with CAF. Thus, molecules for impairing their interactions could be potential therapeutic targets in gastric cancer patients with RHOA mutation. Citation Format: Daye Jeon, Yuri Choi, Seon Jin Lee, Kyung Un Choi, Do Youn Park, Chae Hwa Kwon. Interaction between RHOA mutated gastric cancer cells and cancer associated fibroblasts promotes tumorigenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5112.