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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Nature Portfolio
2020
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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) |
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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 |
work_keys_str_mv |
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