Cargando…
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,...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783303697128751104 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5834702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT hashimotokyoko cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT ochihiroki cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT sunamurasatoko cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT kosakanobuyoshi cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT mabuchiyo cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT fukudatoru cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT yaokenta cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT kandahiroaki cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT aekeisuke cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT okawaatsushi cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT akazawachihiro cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT ochiyatakahiro cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT futakuchimitsuru cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT takedashu cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a AT satoshingo cancersecretedhsamir940inducesanosteoblasticphenotypeinthebonemetastaticmicroenvironmentviatargetingarhgap1andfam134a |