Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric cancer cells
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Tomohiro Arita1, Daisuke Ichikawa1, Hirotaka Konishi1, Shuhei Komatsu1, Atsushi Shiozaki1, Shinpei Ogino1, Yuji Fujita1, Hidekazu Hiramoto1, Junichi Hamada1, Katsutoshi Shoda1, Toshiyuki Kosuga1, Hitoshi Fujiwara1, Kazuma Okamoto1, Eigo Otsuji1
1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
Daisuke Ichikawa, email: [email protected]
Keywords: gastric cancer, exosome, peritoneal metastasis, fibronectin 1, laminin gamma 1
Received: December 20, 2015 Accepted: July 18, 2016 Published: July 28, 2016
Background: Peritoneal metastasis consists of a highly complex series of steps, and the details of the underlying molecular mechanism remain largely unclear. In this study, the effects of tumor-derived exosomes (TEX) on the progression of gastric cancers were investigated in peritoneal metastasis.
Results: TEX were internalized in both mesothelial and gastric cancer cells in a cellular origin non-specific manner. Internalization of TEX into mesothelial cells promoted significant adhesion between mesothelial and gastric cancer cells, and TEX internalization into gastric cancer cells significantly promoted migratory ability, while internalization of mesothelial cell-derived exosomes did not. Expression of adhesion-related molecules, such as fibronectin 1 (FN1) and laminin gamma 1 (LAMC1), were increased in mesothelial cells after internalization of TEX from gastric cancer cell line and malignant pleural effusion.
Methods: TEX were extracted from cell-conditioned medium by ultracentrifugation. The effects of TEX on the malignant potential of gastric cancer were investigated in adhesion, invasion, and proliferation assays. PCR array as well as western blotting were performed to determine the underlying molecular mechanisms. The molecular changes in mesothelial cell after internalization of TEX derived from malignant pleural effusion were also confirmed.
Conclusions: TEX may play a critical role in the development of peritoneal metastasis of gastric cancer, which may be partially due to inducing increased expression of adhesion molecules in mesothelial cells.
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