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Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction

Increased expression of extracellular matrix (ECM) proteins in circulating tumor cells (CTCs) suggests potential function of cancer cell-produced ECM in initiation of cancer cell colonization. Here, we showed that collagen and heat shock protein 47 (Hsp47), a chaperone facilitating collagen secretio...

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Autores principales: Xiong, Gaofeng, Chen, Jie, Zhang, Guoying, Wang, Shike, Kawasaki, Kunito, Zhu, Jieqing, Zhang, Yan, Nagata, Kazuhiro, Li, Zhenyu, Zhou, Binhua P., Xu, Ren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035603/
https://www.ncbi.nlm.nih.gov/pubmed/32015106
http://dx.doi.org/10.1073/pnas.1911951117
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author Xiong, Gaofeng
Chen, Jie
Zhang, Guoying
Wang, Shike
Kawasaki, Kunito
Zhu, Jieqing
Zhang, Yan
Nagata, Kazuhiro
Li, Zhenyu
Zhou, Binhua P.
Xu, Ren
author_facet Xiong, Gaofeng
Chen, Jie
Zhang, Guoying
Wang, Shike
Kawasaki, Kunito
Zhu, Jieqing
Zhang, Yan
Nagata, Kazuhiro
Li, Zhenyu
Zhou, Binhua P.
Xu, Ren
author_sort Xiong, Gaofeng
collection PubMed
description Increased expression of extracellular matrix (ECM) proteins in circulating tumor cells (CTCs) suggests potential function of cancer cell-produced ECM in initiation of cancer cell colonization. Here, we showed that collagen and heat shock protein 47 (Hsp47), a chaperone facilitating collagen secretion and deposition, were highly expressed during the epithelial-mesenchymal transition (EMT) and in CTCs. Hsp47 expression induced mesenchymal phenotypes in mammary epithelial cells (MECs), enhanced platelet recruitment, and promoted lung retention and colonization of cancer cells. Platelet depletion in vivo abolished Hsp47-induced cancer cell retention in the lung, suggesting that Hsp47 promotes cancer cell colonization by enhancing cancer cell–platelet interaction. Using rescue experiments and functional blocking antibodies, we identified type I collagen as the key mediator of Hsp47-induced cancer cell–platelet interaction. We also found that Hsp47-dependent collagen deposition and platelet recruitment facilitated cancer cell clustering and extravasation in vitro. By analyzing DNA/RNA sequencing data generated from human breast cancer tissues, we showed that gene amplification and increased expression of Hsp47 were associated with cancer metastasis. These results suggest that targeting the Hsp47/collagen axis is a promising strategy to block cancer cell–platelet interaction and cancer colonization in secondary organs.
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spelling pubmed-70356032020-02-28 Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction Xiong, Gaofeng Chen, Jie Zhang, Guoying Wang, Shike Kawasaki, Kunito Zhu, Jieqing Zhang, Yan Nagata, Kazuhiro Li, Zhenyu Zhou, Binhua P. Xu, Ren Proc Natl Acad Sci U S A Biological Sciences Increased expression of extracellular matrix (ECM) proteins in circulating tumor cells (CTCs) suggests potential function of cancer cell-produced ECM in initiation of cancer cell colonization. Here, we showed that collagen and heat shock protein 47 (Hsp47), a chaperone facilitating collagen secretion and deposition, were highly expressed during the epithelial-mesenchymal transition (EMT) and in CTCs. Hsp47 expression induced mesenchymal phenotypes in mammary epithelial cells (MECs), enhanced platelet recruitment, and promoted lung retention and colonization of cancer cells. Platelet depletion in vivo abolished Hsp47-induced cancer cell retention in the lung, suggesting that Hsp47 promotes cancer cell colonization by enhancing cancer cell–platelet interaction. Using rescue experiments and functional blocking antibodies, we identified type I collagen as the key mediator of Hsp47-induced cancer cell–platelet interaction. We also found that Hsp47-dependent collagen deposition and platelet recruitment facilitated cancer cell clustering and extravasation in vitro. By analyzing DNA/RNA sequencing data generated from human breast cancer tissues, we showed that gene amplification and increased expression of Hsp47 were associated with cancer metastasis. These results suggest that targeting the Hsp47/collagen axis is a promising strategy to block cancer cell–platelet interaction and cancer colonization in secondary organs. National Academy of Sciences 2020-02-18 2020-02-03 /pmc/articles/PMC7035603/ /pubmed/32015106 http://dx.doi.org/10.1073/pnas.1911951117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ 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
Xiong, Gaofeng
Chen, Jie
Zhang, Guoying
Wang, Shike
Kawasaki, Kunito
Zhu, Jieqing
Zhang, Yan
Nagata, Kazuhiro
Li, Zhenyu
Zhou, Binhua P.
Xu, Ren
Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction
title Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction
title_full Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction
title_fullStr Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction
title_full_unstemmed Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction
title_short Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction
title_sort hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035603/
https://www.ncbi.nlm.nih.gov/pubmed/32015106
http://dx.doi.org/10.1073/pnas.1911951117
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