論文

査読有り 国際誌
2018年2月27日

Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A.

Proceedings of the National Academy of Sciences of the United States of America
  • Kyoko Hashimoto
  • ,
  • Hiroki Ochi
  • ,
  • Satoko Sunamura
  • ,
  • Nobuyoshi Kosaka
  • ,
  • Yo Mabuchi
  • ,
  • Toru Fukuda
  • ,
  • Kenta Yao
  • ,
  • Hiroaki Kanda
  • ,
  • Keisuke Ae
  • ,
  • Atsushi Okawa
  • ,
  • Chihiro Akazawa
  • ,
  • Takahiro Ochiya
  • ,
  • Mitsuru Futakuchi
  • ,
  • Shu Takeda
  • ,
  • Shingo Sato

115
9
開始ページ
2204
終了ページ
2209
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1717363115

Bone metastatic lesions are classified as osteoblastic or osteolytic lesions. Prostate and breast cancer patients frequently exhibit osteoblastic-type and osteolytic-type bone metastasis, respectively. In metastatic lesions, tumor cells interact with many different cell types, including osteoblasts, osteoclasts, and mesenchymal stem cells, resulting in an osteoblastic or osteolytic phenotype. However, the mechanisms responsible for the modification of bone remodeling have not been fully elucidated. MicroRNAs (miRNAs) are transferred between cells via exosomes and serve as intercellular communication tools, and numerous studies have demonstrated that cancer-secreted miRNAs are capable of modifying the tumor microenvironment. Thus, cancer-secreted miRNAs can induce an osteoblastic or osteolytic phenotype in the bone metastatic microenvironment. In this study, we performed a comprehensive expression analysis of exosomal miRNAs secreted by several human cancer cell lines and identified eight types of human miRNAs that were highly expressed in exosomes from osteoblastic phenotype-inducing prostate cancer cell lines. One of these miRNAs, hsa-miR-940, significantly promoted the osteogenic differentiation of human mesenchymal stem cells in vitro by targeting ARHGAP1 and FAM134A Interestingly, although MDA-MB-231 breast cancer cells are commonly known as an osteolytic phenotype-inducing cancer cell line, the implantation of miR-940-overexpressing MDA-MB-231 cells induced extensive osteoblastic lesions in the resulting tumors by facilitating the osteogenic differentiation of host mesenchymal cells. Our results suggest that the phenotypes of bone metastases can be induced by miRNAs secreted by cancer cells in the bone microenvironment.

リンク情報
DOI
https://doi.org/10.1073/pnas.1717363115
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29440427
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834702

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