Cargando…

Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan

Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs co...

Descripción completa

Detalles Bibliográficos
Autores principales: Maishi, Nako, Ohba, Yusuke, Akiyama, Kosuke, Ohga, Noritaka, Hamada, Jun-ichi, Nagao-Kitamoto, Hiroko, Alam, Mohammad Towfik, Yamamoto, Kazuyuki, Kawamoto, Taisuke, Inoue, Nobuo, Taketomi, Akinobu, Shindoh, Masanobu, Hida, Yasuhiro, Hida, Kyoko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904795/
https://www.ncbi.nlm.nih.gov/pubmed/27295191
http://dx.doi.org/10.1038/srep28039
_version_ 1782437201986977792
author Maishi, Nako
Ohba, Yusuke
Akiyama, Kosuke
Ohga, Noritaka
Hamada, Jun-ichi
Nagao-Kitamoto, Hiroko
Alam, Mohammad Towfik
Yamamoto, Kazuyuki
Kawamoto, Taisuke
Inoue, Nobuo
Taketomi, Akinobu
Shindoh, Masanobu
Hida, Yasuhiro
Hida, Kyoko
author_facet Maishi, Nako
Ohba, Yusuke
Akiyama, Kosuke
Ohga, Noritaka
Hamada, Jun-ichi
Nagao-Kitamoto, Hiroko
Alam, Mohammad Towfik
Yamamoto, Kazuyuki
Kawamoto, Taisuke
Inoue, Nobuo
Taketomi, Akinobu
Shindoh, Masanobu
Hida, Yasuhiro
Hida, Kyoko
author_sort Maishi, Nako
collection PubMed
description Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis.
format Online
Article
Text
id pubmed-4904795
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-49047952016-06-14 Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan Maishi, Nako Ohba, Yusuke Akiyama, Kosuke Ohga, Noritaka Hamada, Jun-ichi Nagao-Kitamoto, Hiroko Alam, Mohammad Towfik Yamamoto, Kazuyuki Kawamoto, Taisuke Inoue, Nobuo Taketomi, Akinobu Shindoh, Masanobu Hida, Yasuhiro Hida, Kyoko Sci Rep Article Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. Nature Publishing Group 2016-06-13 /pmc/articles/PMC4904795/ /pubmed/27295191 http://dx.doi.org/10.1038/srep28039 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Maishi, Nako
Ohba, Yusuke
Akiyama, Kosuke
Ohga, Noritaka
Hamada, Jun-ichi
Nagao-Kitamoto, Hiroko
Alam, Mohammad Towfik
Yamamoto, Kazuyuki
Kawamoto, Taisuke
Inoue, Nobuo
Taketomi, Akinobu
Shindoh, Masanobu
Hida, Yasuhiro
Hida, Kyoko
Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan
title Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan
title_full Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan
title_fullStr Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan
title_full_unstemmed Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan
title_short Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan
title_sort tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904795/
https://www.ncbi.nlm.nih.gov/pubmed/27295191
http://dx.doi.org/10.1038/srep28039
work_keys_str_mv AT maishinako tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT ohbayusuke tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT akiyamakosuke tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT ohganoritaka tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT hamadajunichi tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT nagaokitamotohiroko tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT alammohammadtowfik tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT yamamotokazuyuki tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT kawamototaisuke tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT inouenobuo tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT taketomiakinobu tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT shindohmasanobu tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT hidayasuhiro tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan
AT hidakyoko tumourendothelialcellsinhighmetastatictumourspromotemetastasisviaepigeneticdysregulationofbiglycan