Abstract 3078: The role of extracellular vesicles in chemotherapy resistance in gastric cancer

Abstract

Abstract Gastric adenocarcinoma (GAd) is the fourth most common cancer and the second cause of cancer death in the world. Chemotherapy has been largely used to treat this disease however acquired drug resistance is a common event and is associated to the development of new more aggressive clones of tumor cells. Herein, a gastric adenocarcinoma cell line (AGS) resistant to the 5-fluorouracil (rAGS-FU) was generated in order to establish mechanisms associated to acquire drug resistance. In the presence of 5-FU (10μM) resistant cells show a 2-3 times higher proliferation ratio than parental cells, a plating efficiency of 38% compared to 1% of parental cells and a higher invasive phenotype. Remarkable, when compared to parental cells, rAGS-FU resistant cells secreted 2-3 times more extracellular vesicles, EVs (85-175nm). When parental cells were treated with EVs from rAGS-5-FU resistant cells they acquired the same phenotype of the latter cells regarding higher proliferation, plating efficiency and invasion. The proteomic analysis of parental and rAGS-FU cells showed 306 differentially expressed proteins, while 66 differentially expressed proteins were found when EVs secreted from these cells were compared. Our data suggest that cells resistant to chemotherapy have a more aggressive phenotype and are able to transfer these characteristics to non-resistant cells. These findings point to mechanisms of chemoresistance mediated by components that are carried from cell to cell by EVs, what may indicate novel approaches that can be addressed to impair drug resistance and improve treatment response. Supported by FAPESP Citation Format: Edson Cassinela, Michele C. Landemberger, Gabriela P. de Oliveira, Vilma Regina Martins. The role of extracellular vesicles in chemotherapy resistance in gastric cancer [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 3078. doi:10.1158/1538-7445.AM2017-3078