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Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab

Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms rema...

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Autores principales: Mitsuhashi, Atsushi, Goto, Hisatsugu, Saijo, Atsuro, Trung, Van The, Aono, Yoshinori, Ogino, Hirokazu, Kuramoto, Takuya, Tabata, Sho, Uehara, Hisanori, Izumi, Keisuke, Yoshida, Mitsuteru, Kobayashi, Hiroaki, Takahashi, Hidefusa, Gotoh, Masashi, Kakiuchi, Soji, Hanibuchi, Masaki, Yano, Seiji, Yokomise, Hiroyasu, Sakiyama, Shoji, Nishioka, Yasuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686833/
https://www.ncbi.nlm.nih.gov/pubmed/26635184
http://dx.doi.org/10.1038/ncomms9792
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author Mitsuhashi, Atsushi
Goto, Hisatsugu
Saijo, Atsuro
Trung, Van The
Aono, Yoshinori
Ogino, Hirokazu
Kuramoto, Takuya
Tabata, Sho
Uehara, Hisanori
Izumi, Keisuke
Yoshida, Mitsuteru
Kobayashi, Hiroaki
Takahashi, Hidefusa
Gotoh, Masashi
Kakiuchi, Soji
Hanibuchi, Masaki
Yano, Seiji
Yokomise, Hiroyasu
Sakiyama, Shoji
Nishioka, Yasuhiko
author_facet Mitsuhashi, Atsushi
Goto, Hisatsugu
Saijo, Atsuro
Trung, Van The
Aono, Yoshinori
Ogino, Hirokazu
Kuramoto, Takuya
Tabata, Sho
Uehara, Hisanori
Izumi, Keisuke
Yoshida, Mitsuteru
Kobayashi, Hiroaki
Takahashi, Hidefusa
Gotoh, Masashi
Kakiuchi, Soji
Hanibuchi, Masaki
Yano, Seiji
Yokomise, Hiroyasu
Sakiyama, Shoji
Nishioka, Yasuhiko
author_sort Mitsuhashi, Atsushi
collection PubMed
description Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive cells, contribute to the acquired resistance to bevacizumab. In mouse models of malignant pleural mesothelioma and lung cancer, fibrocyte-like cells mediate the resistance to bevacizumab as the main producer of fibroblast growth factor 2. In clinical specimens of lung cancer, the number of fibrocyte-like cells is significantly increased in bevacizumab-treated tumours, and correlates with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocyte-like cells as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy.
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spelling pubmed-46868332016-01-07 Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab Mitsuhashi, Atsushi Goto, Hisatsugu Saijo, Atsuro Trung, Van The Aono, Yoshinori Ogino, Hirokazu Kuramoto, Takuya Tabata, Sho Uehara, Hisanori Izumi, Keisuke Yoshida, Mitsuteru Kobayashi, Hiroaki Takahashi, Hidefusa Gotoh, Masashi Kakiuchi, Soji Hanibuchi, Masaki Yano, Seiji Yokomise, Hiroyasu Sakiyama, Shoji Nishioka, Yasuhiko Nat Commun Article Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive cells, contribute to the acquired resistance to bevacizumab. In mouse models of malignant pleural mesothelioma and lung cancer, fibrocyte-like cells mediate the resistance to bevacizumab as the main producer of fibroblast growth factor 2. In clinical specimens of lung cancer, the number of fibrocyte-like cells is significantly increased in bevacizumab-treated tumours, and correlates with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocyte-like cells as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy. Nature Publishing Group 2015-12-04 /pmc/articles/PMC4686833/ /pubmed/26635184 http://dx.doi.org/10.1038/ncomms9792 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 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
Mitsuhashi, Atsushi
Goto, Hisatsugu
Saijo, Atsuro
Trung, Van The
Aono, Yoshinori
Ogino, Hirokazu
Kuramoto, Takuya
Tabata, Sho
Uehara, Hisanori
Izumi, Keisuke
Yoshida, Mitsuteru
Kobayashi, Hiroaki
Takahashi, Hidefusa
Gotoh, Masashi
Kakiuchi, Soji
Hanibuchi, Masaki
Yano, Seiji
Yokomise, Hiroyasu
Sakiyama, Shoji
Nishioka, Yasuhiko
Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab
title Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab
title_full Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab
title_fullStr Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab
title_full_unstemmed Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab
title_short Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab
title_sort fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686833/
https://www.ncbi.nlm.nih.gov/pubmed/26635184
http://dx.doi.org/10.1038/ncomms9792
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