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Abstract 5219: Effect of extracellular vesicles from gastric cancer cells on the morphologic and genetic changes of peritoneal mesothelial cells

Background: Gastric cancer is a major cause of cancer death, particularly on the basis of peritoneal metastasis. Human scirrhous gastric carcinoma (SGC), diffusely infiltrating carcinoma, or Borrman type 4 also known as linitis plastica-type carcinoma is characterized by rapid cancer cell infiltration and proliferation accompanied by extensive stromal fibrosis. SGC account for about 10% of all gastric carcinomas, and carry an extremely worse prognosis than other types of gastric carcinoma, reflecting their frequent peritoneal metastasis. We previously reported that SGC cells (“seed”) might change the peritoneum to favorable environment, so-called pre-metastatic niche (“soil”), (Cancer 77:1668-75, 1996). Recently, it has been clarified that extracellular vesicles (EVs) play an important role for cell-cell interactions. In this study, we investigated the effect of EVs from SGC cells on the pre-metastatic niche formation of the peritoneum. Methods: A SGC cell line, OCUM-2MD3, OCUM-12, KATO-III, gastric cancer cell line, MKN74, MKN45, and peritoneal mesothelial cells (PM cells) were used. PKH26-labeled EVs from OCUM-2MD3 cells were intravenously injected into nude mice, and the distribution of EVs was examined by a fluorescence microscope. The morphology of PM cells was investigated in the addiction of EVs from various gastric cancer cell lines using a phase-contrast microscope. And gene expression was examined by RT-PCR in the presence or absence of EVs from OCUM-2MD3. Clinical significance of EVs markers CD9 and CD63 was immunohistochemically evaluated using 63 human gastric cancer specimens. Results: PKH26-labeled EVs were frequently found in the peritoneum, stomach and liver, but rare in lung and brain of mice. Peritoneal mesothelial cells uptake EVs of gastric cancer cells and change morphology from cobblestone shape to spindle shape in vitro. mRNA expression level of MMPs and integrins in PM cells was increased following the addiction of EVs, in compared with the control. The high expression of CD9 and CD63 was significantly correlated with distant metastasis. Conclusion: EVs from gastric cancer cells might induce a pre-metastatic niche at peritoneum by the morphologic and genetic changes of mesothelial cells. Citation Format: Tomohisa Okuno, Masakazu Yashiro, Shingo Togano, Kenji Kuroda, Yuichiro Miki, Hiroaki Kasashima, Kosei Hirakawa, Masaichi Ohira. Effect of extracellular vesicles from gastric cancer cells on the morphologic and genetic changes of peritoneal mesothelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5219.