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Integrated analyses of single-cell transcriptomics identify metastasis-associated myeloid subpopulations in breast cancer lung metastasis

Lung metastasis of breast cancer is closely associated with patient morbidity and mortality, which correlates with myeloid cells in the lung microenvironment. However, the heterogeneity and specificity of metastasis-associated myeloid cells have not been fully established in lung metastasis. Here, b...

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Autores principales: Huang, Zhen, Bu, Dawei, Yang, Nan, Huang, Wenwen, Zhang, Liyin, Li, Xiaoxue, Ding, Bi-Sen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361816/
https://www.ncbi.nlm.nih.gov/pubmed/37483625
http://dx.doi.org/10.3389/fimmu.2023.1180402
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author Huang, Zhen
Bu, Dawei
Yang, Nan
Huang, Wenwen
Zhang, Liyin
Li, Xiaoxue
Ding, Bi-Sen
author_facet Huang, Zhen
Bu, Dawei
Yang, Nan
Huang, Wenwen
Zhang, Liyin
Li, Xiaoxue
Ding, Bi-Sen
author_sort Huang, Zhen
collection PubMed
description Lung metastasis of breast cancer is closely associated with patient morbidity and mortality, which correlates with myeloid cells in the lung microenvironment. However, the heterogeneity and specificity of metastasis-associated myeloid cells have not been fully established in lung metastasis. Here, by integrating and analyzing single-cell transcriptomics, we found that myeloid subpopulations (Tppp3 (+) monocytes, Isg15 (+) macrophages, Ifit3 (+) neutrophils, and Il12b (+) DCs) play critical roles in the formation and development of the metastatic niche. Gene enrichment analyses indicate that several tumor-promoting pathways should be responsible for the process, including angiogenesis (Anxa1 and Anxa2 by Tppp3 (+) monocytes), immunosuppression (Isg15 and Cxcl10 by Isg15 (+) macrophages; Il12b and Ccl22 by Il12b (+) DCs), and tumor growth and metastasis (Isg15 and Isg20 by Ifit3 (+) neutrophils). Furthermore, we have validated these subpopulations in lung microenvironment of MMTV-PyVT transgenic mice and verified their association with poor progression of human breast cancer. Also, our results elucidated a crosstalk network among four myeloid subpopulations by cell-cell communication analysis. This study, therefore, highlights the crucial role of myeloid cells in lung metastasis and provides insights into underlying molecular mechanisms, which pave the way for therapeutic interventions in breast cancer metastasis to lung.
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spelling pubmed-103618162023-07-22 Integrated analyses of single-cell transcriptomics identify metastasis-associated myeloid subpopulations in breast cancer lung metastasis Huang, Zhen Bu, Dawei Yang, Nan Huang, Wenwen Zhang, Liyin Li, Xiaoxue Ding, Bi-Sen Front Immunol Immunology Lung metastasis of breast cancer is closely associated with patient morbidity and mortality, which correlates with myeloid cells in the lung microenvironment. However, the heterogeneity and specificity of metastasis-associated myeloid cells have not been fully established in lung metastasis. Here, by integrating and analyzing single-cell transcriptomics, we found that myeloid subpopulations (Tppp3 (+) monocytes, Isg15 (+) macrophages, Ifit3 (+) neutrophils, and Il12b (+) DCs) play critical roles in the formation and development of the metastatic niche. Gene enrichment analyses indicate that several tumor-promoting pathways should be responsible for the process, including angiogenesis (Anxa1 and Anxa2 by Tppp3 (+) monocytes), immunosuppression (Isg15 and Cxcl10 by Isg15 (+) macrophages; Il12b and Ccl22 by Il12b (+) DCs), and tumor growth and metastasis (Isg15 and Isg20 by Ifit3 (+) neutrophils). Furthermore, we have validated these subpopulations in lung microenvironment of MMTV-PyVT transgenic mice and verified their association with poor progression of human breast cancer. Also, our results elucidated a crosstalk network among four myeloid subpopulations by cell-cell communication analysis. This study, therefore, highlights the crucial role of myeloid cells in lung metastasis and provides insights into underlying molecular mechanisms, which pave the way for therapeutic interventions in breast cancer metastasis to lung. Frontiers Media S.A. 2023-07-07 /pmc/articles/PMC10361816/ /pubmed/37483625 http://dx.doi.org/10.3389/fimmu.2023.1180402 Text en Copyright © 2023 Huang, Bu, Yang, Huang, Zhang, Li and Ding https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Huang, Zhen
Bu, Dawei
Yang, Nan
Huang, Wenwen
Zhang, Liyin
Li, Xiaoxue
Ding, Bi-Sen
Integrated analyses of single-cell transcriptomics identify metastasis-associated myeloid subpopulations in breast cancer lung metastasis
title Integrated analyses of single-cell transcriptomics identify metastasis-associated myeloid subpopulations in breast cancer lung metastasis
title_full Integrated analyses of single-cell transcriptomics identify metastasis-associated myeloid subpopulations in breast cancer lung metastasis
title_fullStr Integrated analyses of single-cell transcriptomics identify metastasis-associated myeloid subpopulations in breast cancer lung metastasis
title_full_unstemmed Integrated analyses of single-cell transcriptomics identify metastasis-associated myeloid subpopulations in breast cancer lung metastasis
title_short Integrated analyses of single-cell transcriptomics identify metastasis-associated myeloid subpopulations in breast cancer lung metastasis
title_sort integrated analyses of single-cell transcriptomics identify metastasis-associated myeloid subpopulations in breast cancer lung metastasis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361816/
https://www.ncbi.nlm.nih.gov/pubmed/37483625
http://dx.doi.org/10.3389/fimmu.2023.1180402
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