Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric cancer cells

Tomohiro Arita,Hidekazu Hiramoto,Katsutoshi Shoda,Hirotaka Konishi,Shuhei Komatsu,Eigo Otsuji,Daisuke Ichikawa,Atsushi Shiozaki,Kazuma Okamoto,Shinpei Ogino,Yuji Fujita,Toshiyuki Kosuga,Junichi Hamada,Hitoshi Fujiwara

doi:10.18632/oncotarget.10869

Tomohiro Arita, Hidekazu Hiramoto + Show 12 more

Open Access

https://doi.org/10.18632/oncotarget.10869

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Journal: Oncotarget	Publication Date: Jul 28, 2016
Citations: 62	License type: cc-by

Affiliation: Kyoto Prefectural University of Medicine

Abstract

BackgroundPeritoneal 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.ResultsTEX 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.MethodsTEX 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.ConclusionsTEX 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.

Highlights

Peritoneal metastasis is one of the most common patterns of recurrence in gastric cancer patients [1]
tumor-derived exosomes (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
We investigated the possible involvement of TEX on the development of peritoneal dissemination by analyzing the effects of TEX on the adhesive and invasive abilities of tumor and mesothelial cells

Summary

Introduction

Peritoneal metastasis is one of the most common patterns of recurrence in gastric cancer patients [1]. Formation of peritoneal metastasis consists of a highly complex series of mechanisms, and the details of these steps remain largely unknown. Various factors, including tumor and host factors, have been recognized as playing some roles in metastasis formation. Serosal involvement by the primary tumor and subsequent intraperitoneal release of cancer cells are crucially important factors for metastatic formation. Presence of intraperitoneal free cancer cells does not necessarily indicate peritoneal dissemination [2], and several other factors, such as adhesion factors of the cancer cells and the host immune system, are involved in the peritoneal metastatic process [3,4,5,6]. Peritoneal metastasis consists of a highly complex series of steps, and the details of the underlying molecular mechanism remain largely unclear. The effects of tumor-derived exosomes (TEX) on the progression of gastric cancers were investigated in peritoneal metastasis

Methods

Results

Conclusion