Abstract B48: Proteomic analysis of extracellular vesicles from resistant gastric cancer cell line

Abstract

Abstract Background: Gastric cancer is the fourth most common cause of cancer death worldwide and one of the tumors with higher mortality rates in Brazil. Chemotherapy is one of the major treatments for gastric cancer, but drug resistance limits the effectiveness, resulting in treatment failure. The mechanisms of gastric cancer pathogenesis are largely unknown, as is what causes limitations in the personalized treatment. Neoadjuvant therapy has been largely applied in these tumors because it can improve tumor resectability and survival of patients. However, tumors can develop resistance during chemotherapy, or this resistance can be present intrinsically before chemotherapy. Indeed, mechanisms associated to chemotherapy resistance in gastric cancer are complex and multifactorial; understanding the variety of these factors that are involved in chemoresistance is of great relevance. Materials and Methods: Gastric adenocarcinoma cell line (AGS) was treated with increased concentration of 5-fluorouracil to generate a resistant cell (rAGS_FU). Extracellular vesicles (EVs) secreted from AGS and rAGS_FU cell lines were isolated by ultracentrifugation, quantified, and evaluated regarding their aggressiveness through invasion and colony assays. Proteomics analysis of EVs and secreting cells were performed to identify potential markers for chemotherapy resistance in gastric cancer cell lines. Results: We found proteins involved in resistance to chemotherapy upregulated in EVs derived from resistant cells; parental cells treated with EVs derived from resistant cells were able to promote high colony formation and increased invasion potential. Thus, cells resistant to chemotherapy have a more aggressive phenotype and are able to transfer these acquired characteristics to the nonresistant ones using EVs. We compared the proteomes of EVs derived from the two cell lines and revealed important pathways that can be associated with chemoresistance in gastric cancers. Conclusion: It is crucial to understand these chemoresistance mechanisms and develop efficient treatment strategies to overcome them. A deep investigation of these data is needed to understand and create new opportunities for the discovery of new biomarkers of response to chemotherapy in gastric cancers and contribute to the better understanding of the biologic role of molecules shuttled by EVs. Citation Format: Edson Kuatelela Cassinela, Grabriela Pintar Oliveira, Michele Christine Landemberger, Vilma Regina Martins. Proteomic analysis of extracellular vesicles from resistant gastric cancer cell line [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B48.