Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis

Abstract The most common site of breast cancer metastasis is the bone, occurring in approximately 70% of patients with advanced disease. Bone metastasis is associated with severe morbidities and high mortality. Therefore, deeper understanding of the mechanisms that enable bone-metastatic relapse are...

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Autores principales: Lea Monteran, Nour Ershaid, Idan Sabah, Ibrahim Fahoum, Yael Zait, Ophir Shani, Noam Cohen, Anat Eldar-Boock, Ronit Satchi-Fainaro, Neta Erez
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Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/dbff80225c2243a0816be0111a06e98b
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spelling oai:doaj.org-article:dbff80225c2243a0816be0111a06e98b2021-12-02T18:50:49ZBone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis10.1038/s41598-020-70788-32045-2322https://doaj.org/article/dbff80225c2243a0816be0111a06e98b2020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70788-3https://doaj.org/toc/2045-2322Abstract The most common site of breast cancer metastasis is the bone, occurring in approximately 70% of patients with advanced disease. Bone metastasis is associated with severe morbidities and high mortality. Therefore, deeper understanding of the mechanisms that enable bone-metastatic relapse are urgently needed. We report the establishment and characterization of a bone-seeking variant of breast cancer cells that spontaneously forms aggressive bone metastases following surgical resection of primary tumor. We characterized the modifications in the immune milieu during early and late stages of metastatic relapse and found that the formation of bone metastases is associated with systemic changes, as well as modifications of the bone microenvironment towards an immune suppressive milieu. Furthermore, we characterized the intrinsic changes in breast cancer cells that facilitate bone-tropism and found that they acquire mesenchymal and osteomimetic features. This model provides a clinically relevant platform to study the functional interactions between breast cancer cells and the bone microenvironment, in an effort to identify novel targets for intervention.Lea MonteranNour ErshaidIdan SabahIbrahim FahoumYael ZaitOphir ShaniNoam CohenAnat Eldar-BoockRonit Satchi-FainaroNeta ErezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lea Monteran
Nour Ershaid
Idan Sabah
Ibrahim Fahoum
Yael Zait
Ophir Shani
Noam Cohen
Anat Eldar-Boock
Ronit Satchi-Fainaro
Neta Erez
Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis
description Abstract The most common site of breast cancer metastasis is the bone, occurring in approximately 70% of patients with advanced disease. Bone metastasis is associated with severe morbidities and high mortality. Therefore, deeper understanding of the mechanisms that enable bone-metastatic relapse are urgently needed. We report the establishment and characterization of a bone-seeking variant of breast cancer cells that spontaneously forms aggressive bone metastases following surgical resection of primary tumor. We characterized the modifications in the immune milieu during early and late stages of metastatic relapse and found that the formation of bone metastases is associated with systemic changes, as well as modifications of the bone microenvironment towards an immune suppressive milieu. Furthermore, we characterized the intrinsic changes in breast cancer cells that facilitate bone-tropism and found that they acquire mesenchymal and osteomimetic features. This model provides a clinically relevant platform to study the functional interactions between breast cancer cells and the bone microenvironment, in an effort to identify novel targets for intervention.
format article
author Lea Monteran
Nour Ershaid
Idan Sabah
Ibrahim Fahoum
Yael Zait
Ophir Shani
Noam Cohen
Anat Eldar-Boock
Ronit Satchi-Fainaro
Neta Erez
author_facet Lea Monteran
Nour Ershaid
Idan Sabah
Ibrahim Fahoum
Yael Zait
Ophir Shani
Noam Cohen
Anat Eldar-Boock
Ronit Satchi-Fainaro
Neta Erez
author_sort Lea Monteran
title Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis
title_short Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis
title_full Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis
title_fullStr Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis
title_full_unstemmed Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis
title_sort bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/dbff80225c2243a0816be0111a06e98b
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