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

Abstract

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.

• Authors: Tomohiro Arita, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Atsushi Shiozaki, Shinpei Ogino, Yuji Fujita, Hidekazu Hiramoto, Junichi Hamada, Katsutoshi Shoda, Toshiyuki Kosuga, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 35 Pg. 56855-56863 (Aug 30 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27487135 (Publication Type: Journal Article)

Chemical References

• Culture Media, Conditioned
• Cytokines
• FN1 protein, human
• Fibronectins
• Laminin
• laminin gamma 1

Topics

• Cell Adhesion
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Culture Media, Conditioned (chemistry)
• Cytokines (metabolism)
• Disease Progression
• Epithelium (metabolism)
• Exosomes (metabolism)
• Fibronectins
• Humans
• Laminin (metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Peritoneal Neoplasms (metabolism, secondary)
• Peritoneum (pathology)
• Phenotype
• Pleural Effusion, Malignant
• Polymerase Chain Reaction
• Stomach (pathology)
• Stomach Neoplasms (metabolism, pathology)
• Ultracentrifugation