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Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling

Dissemination of tumour cells to the bone marrow is an early event in breast cancer, however cells may lie dormant for many years before bone metastases develop. Treatment for bone metastases is not curative, therefore new adjuvant therapies which prevent the colonisation of disseminated cells into...

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Autores principales: Eyre, Rachel, Alférez, Denis G., Santiago-Gómez, Angélica, Spence, Kath, McConnell, James C., Hart, Claire, Simões, Bruno M., Lefley, Diane, Tulotta, Claudia, Storer, Joanna, Gurney, Austin, Clarke, Noel, Brown, Mick, Howell, Sacha J., Sims, Andrew H., Farnie, Gillian, Ottewell, Penelope D., Clarke, Robert B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825219/
https://www.ncbi.nlm.nih.gov/pubmed/31676788
http://dx.doi.org/10.1038/s41467-019-12807-0
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author Eyre, Rachel
Alférez, Denis G.
Santiago-Gómez, Angélica
Spence, Kath
McConnell, James C.
Hart, Claire
Simões, Bruno M.
Lefley, Diane
Tulotta, Claudia
Storer, Joanna
Gurney, Austin
Clarke, Noel
Brown, Mick
Howell, Sacha J.
Sims, Andrew H.
Farnie, Gillian
Ottewell, Penelope D.
Clarke, Robert B.
author_facet Eyre, Rachel
Alférez, Denis G.
Santiago-Gómez, Angélica
Spence, Kath
McConnell, James C.
Hart, Claire
Simões, Bruno M.
Lefley, Diane
Tulotta, Claudia
Storer, Joanna
Gurney, Austin
Clarke, Noel
Brown, Mick
Howell, Sacha J.
Sims, Andrew H.
Farnie, Gillian
Ottewell, Penelope D.
Clarke, Robert B.
author_sort Eyre, Rachel
collection PubMed
description Dissemination of tumour cells to the bone marrow is an early event in breast cancer, however cells may lie dormant for many years before bone metastases develop. Treatment for bone metastases is not curative, therefore new adjuvant therapies which prevent the colonisation of disseminated cells into metastatic lesions are required. There is evidence that cancer stem cells (CSCs) within breast tumours are capable of metastasis, but the mechanism by which these colonise bone is unknown. Here, we establish that bone marrow-derived IL1β stimulates breast cancer cell colonisation in the bone by inducing intracellular NFkB and CREB signalling in breast cancer cells, leading to autocrine Wnt signalling and CSC colony formation. Importantly, we show that inhibition of this pathway prevents both CSC colony formation in the bone environment, and bone metastasis. These findings establish that targeting IL1β-NFKB/CREB-Wnt signalling should be considered for adjuvant therapy to prevent breast cancer bone metastasis.
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spelling pubmed-68252192019-11-04 Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling Eyre, Rachel Alférez, Denis G. Santiago-Gómez, Angélica Spence, Kath McConnell, James C. Hart, Claire Simões, Bruno M. Lefley, Diane Tulotta, Claudia Storer, Joanna Gurney, Austin Clarke, Noel Brown, Mick Howell, Sacha J. Sims, Andrew H. Farnie, Gillian Ottewell, Penelope D. Clarke, Robert B. Nat Commun Article Dissemination of tumour cells to the bone marrow is an early event in breast cancer, however cells may lie dormant for many years before bone metastases develop. Treatment for bone metastases is not curative, therefore new adjuvant therapies which prevent the colonisation of disseminated cells into metastatic lesions are required. There is evidence that cancer stem cells (CSCs) within breast tumours are capable of metastasis, but the mechanism by which these colonise bone is unknown. Here, we establish that bone marrow-derived IL1β stimulates breast cancer cell colonisation in the bone by inducing intracellular NFkB and CREB signalling in breast cancer cells, leading to autocrine Wnt signalling and CSC colony formation. Importantly, we show that inhibition of this pathway prevents both CSC colony formation in the bone environment, and bone metastasis. These findings establish that targeting IL1β-NFKB/CREB-Wnt signalling should be considered for adjuvant therapy to prevent breast cancer bone metastasis. Nature Publishing Group UK 2019-11-01 /pmc/articles/PMC6825219/ /pubmed/31676788 http://dx.doi.org/10.1038/s41467-019-12807-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Eyre, Rachel
Alférez, Denis G.
Santiago-Gómez, Angélica
Spence, Kath
McConnell, James C.
Hart, Claire
Simões, Bruno M.
Lefley, Diane
Tulotta, Claudia
Storer, Joanna
Gurney, Austin
Clarke, Noel
Brown, Mick
Howell, Sacha J.
Sims, Andrew H.
Farnie, Gillian
Ottewell, Penelope D.
Clarke, Robert B.
Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
title Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
title_full Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
title_fullStr Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
title_full_unstemmed Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
title_short Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
title_sort microenvironmental il1β promotes breast cancer metastatic colonisation in the bone via activation of wnt signalling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825219/
https://www.ncbi.nlm.nih.gov/pubmed/31676788
http://dx.doi.org/10.1038/s41467-019-12807-0
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