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Exosomal transfer of functional small RNAs mediates cancer-stroma communication in human endometrium.

Authors
  • Maida, Yoshiko1, 2
  • Takakura, Masahiro1
  • Nishiuchi, Takumi3
  • Yoshimoto, Tanihiro2
  • Kyo, Satoru4
  • 1 Department of Obstetrics and Gynecology, Kanazawa University School of Medicine, Kanazawa, Japan. , (Japan)
  • 2 Department of Molecular Pharmacology, Kanazawa University School of Medicine, Kanazawa, Japan. , (Japan)
  • 3 Institute for Gene Research, Kanazawa University Advanced Science Research Center, Kanazawa, Japan. , (Japan)
  • 4 Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan. , (Japan)
Type
Published Article
Journal
Cancer Medicine
Publisher
Wiley
Publication Date
Feb 01, 2016
Volume
5
Issue
2
Pages
304–314
Identifiers
DOI: 10.1002/cam4.545
PMID: 26700550
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Exosomes are small membrane vesicles secreted from a variety of cell types. Recent evidence indicates that human cells communicate with each other by exchanging exosomes. Cancer cells closely interact with neighboring stromal cells, and together they cooperatively promote disease via bidirectional communication. Here, we investigated whether exosomes can play roles in intercellular communication between cancer cells and neighboring fibroblasts. Endometrial fibroblasts were isolated from normal endometrial tissues and from endometrial cancer tissues, and cell-to-cell transfer of endometrial cancer cell line Ishikawa-derived exosomes was examined. The isolated fibroblasts were cultured in conditioned media from CD63-GFP-expressing Ishikawa cells, and we found that GFP-positive exosomes were transferred from Ishikawa cells to the fibroblasts. Next, we introduced a shRNA for a luciferase gene into Ishikawa cells. This shRNA was encapsulated into exosomes, was transferred to the fibroblasts, and then downregulated luciferase expression in the fibroblasts. The mature microRNAs naturally expressed in Ishikawa-derived exosomes were also transported into the endometrial fibroblasts, and they altered the microRNA expression profiles of the fibroblasts. These results indicated that endometrial cancer cells could transmit small regulatory RNAs to endometrial fibroblasts via exosomes. Our findings document a previously unknown mode of intercellular communication between cancer cells and related fibroblasts in human endometrium. © 2015 The Author. Cancer Medicine published by John Wiley & Sons Ltd.

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