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

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,...

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Autores principales: Hashimoto, Kyoko, Ochi, Hiroki, Sunamura, Satoko, Kosaka, Nobuyoshi, Mabuchi, Yo, Fukuda, Toru, Yao, Kenta, Kanda, Hiroaki, Ae, Keisuke, Okawa, Atsushi, Akazawa, Chihiro, Ochiya, Takahiro, Futakuchi, Mitsuru, Takeda, Shu, Sato, Shingo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834702/
https://www.ncbi.nlm.nih.gov/pubmed/29440427
http://dx.doi.org/10.1073/pnas.1717363115
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author Hashimoto, Kyoko
Ochi, Hiroki
Sunamura, Satoko
Kosaka, Nobuyoshi
Mabuchi, Yo
Fukuda, Toru
Yao, Kenta
Kanda, Hiroaki
Ae, Keisuke
Okawa, Atsushi
Akazawa, Chihiro
Ochiya, Takahiro
Futakuchi, Mitsuru
Takeda, Shu
Sato, Shingo
author_facet Hashimoto, Kyoko
Ochi, Hiroki
Sunamura, Satoko
Kosaka, Nobuyoshi
Mabuchi, Yo
Fukuda, Toru
Yao, Kenta
Kanda, Hiroaki
Ae, Keisuke
Okawa, Atsushi
Akazawa, Chihiro
Ochiya, Takahiro
Futakuchi, Mitsuru
Takeda, Shu
Sato, Shingo
author_sort Hashimoto, Kyoko
collection PubMed
description 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.
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spelling pubmed-58347022018-03-06 Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A Hashimoto, Kyoko Ochi, Hiroki Sunamura, Satoko Kosaka, Nobuyoshi Mabuchi, Yo Fukuda, Toru Yao, Kenta Kanda, Hiroaki Ae, Keisuke Okawa, Atsushi Akazawa, Chihiro Ochiya, Takahiro Futakuchi, Mitsuru Takeda, Shu Sato, Shingo Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2018-02-27 2018-02-12 /pmc/articles/PMC5834702/ /pubmed/29440427 http://dx.doi.org/10.1073/pnas.1717363115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Hashimoto, Kyoko
Ochi, Hiroki
Sunamura, Satoko
Kosaka, Nobuyoshi
Mabuchi, Yo
Fukuda, Toru
Yao, Kenta
Kanda, Hiroaki
Ae, Keisuke
Okawa, Atsushi
Akazawa, Chihiro
Ochiya, Takahiro
Futakuchi, Mitsuru
Takeda, Shu
Sato, Shingo
Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A
title Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A
title_full Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A
title_fullStr Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A
title_full_unstemmed Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A
title_short Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A
title_sort cancer-secreted hsa-mir-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting arhgap1 and fam134a
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834702/
https://www.ncbi.nlm.nih.gov/pubmed/29440427
http://dx.doi.org/10.1073/pnas.1717363115
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