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An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9

BACKGROUND: Breast cancer is highly heterogeneous, suggesting that small but relevant subsets have been under-recognized. Rare and mainly triple-negative breast cancers (TNBCs) were recently found to exhibit tuft cell-like expression profiles, including POU2F3, the tuft cell master regulator. In add...

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Autores principales: Yamada, Yosuke, Simon, Ronald, Iwane, Kosuke, Nakanishi, Yuki, Takeuchi, Yasuhide, Yoshizawa, Akihiko, Takada, Masahiro, Toi, Masakazu, Haga, Hironori, Marx, Alexander, Sauter, Guido
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183142/
https://www.ncbi.nlm.nih.gov/pubmed/37179317
http://dx.doi.org/10.1186/s12885-023-10949-5
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author Yamada, Yosuke
Simon, Ronald
Iwane, Kosuke
Nakanishi, Yuki
Takeuchi, Yasuhide
Yoshizawa, Akihiko
Takada, Masahiro
Toi, Masakazu
Haga, Hironori
Marx, Alexander
Sauter, Guido
author_facet Yamada, Yosuke
Simon, Ronald
Iwane, Kosuke
Nakanishi, Yuki
Takeuchi, Yasuhide
Yoshizawa, Akihiko
Takada, Masahiro
Toi, Masakazu
Haga, Hironori
Marx, Alexander
Sauter, Guido
author_sort Yamada, Yosuke
collection PubMed
description BACKGROUND: Breast cancer is highly heterogeneous, suggesting that small but relevant subsets have been under-recognized. Rare and mainly triple-negative breast cancers (TNBCs) were recently found to exhibit tuft cell-like expression profiles, including POU2F3, the tuft cell master regulator. In addition, immunohistochemistry (IHC) has identified POU2F3-positive cells in the normal human breast, suggesting the presence of tuft cells in this organ. METHODS: Here, we (i) reviewed previously identified POU2F3-positive invasive breast cancers (n = 4) for POU2F3 expression in intraductal cancer components, (ii) investigated a new cohort of invasive breast cancers (n = 1853) by POU2F3-IHC, (iii) explored POU2F3-expressing cells in non-neoplastic breast tissues obtained from women with or without BRCA1 mutations (n = 15), and (iv) reanalyzed publicly available single-cell RNA sequencing (scRNA-seq) data from normal breast cells. RESULTS: Two TNBCs of the four previously reported invasive POU2F3-positive breast cancers contained POU2F3-positive ductal carcinoma in situ (DCIS). In the new cohort of invasive breast cancers, IHC revealed four POU2F3-positive cases, two of which were triple-negative, one luminal-type, and one triple-positive. In addition, another new POU2F3-positive tumor with a triple-negative phenotype was found in daily practice. All non-neoplastic breast tissues contained POU2F3-positive cells, irrespective of BRCA1 status. The scRNA-seq reanalysis confirmed POU2F3-expressing epithelial cells (3.3% of all epithelial cells) and the 17% that co-expressed the other two tuft cell-related markers (SOX9/AVIL or SOX9/GFI1B), which suggested they were bona fide tuft cells. Of note, SOX9 is also known as the “master regulator” of TNBCs. CONCLUSIONS: POU2F3 expression defines small subsets in various breast cancer subtypes, which can be accompanied by DCIS. The mechanistic relationship between POU2F3 and SOX9 in the breast warrants further analysis to enhance our understanding of normal breast physiology and to clarify the significance of the tuft cell-like phenotype for TNBCs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10949-5.
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spelling pubmed-101831422023-05-15 An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9 Yamada, Yosuke Simon, Ronald Iwane, Kosuke Nakanishi, Yuki Takeuchi, Yasuhide Yoshizawa, Akihiko Takada, Masahiro Toi, Masakazu Haga, Hironori Marx, Alexander Sauter, Guido BMC Cancer Research BACKGROUND: Breast cancer is highly heterogeneous, suggesting that small but relevant subsets have been under-recognized. Rare and mainly triple-negative breast cancers (TNBCs) were recently found to exhibit tuft cell-like expression profiles, including POU2F3, the tuft cell master regulator. In addition, immunohistochemistry (IHC) has identified POU2F3-positive cells in the normal human breast, suggesting the presence of tuft cells in this organ. METHODS: Here, we (i) reviewed previously identified POU2F3-positive invasive breast cancers (n = 4) for POU2F3 expression in intraductal cancer components, (ii) investigated a new cohort of invasive breast cancers (n = 1853) by POU2F3-IHC, (iii) explored POU2F3-expressing cells in non-neoplastic breast tissues obtained from women with or without BRCA1 mutations (n = 15), and (iv) reanalyzed publicly available single-cell RNA sequencing (scRNA-seq) data from normal breast cells. RESULTS: Two TNBCs of the four previously reported invasive POU2F3-positive breast cancers contained POU2F3-positive ductal carcinoma in situ (DCIS). In the new cohort of invasive breast cancers, IHC revealed four POU2F3-positive cases, two of which were triple-negative, one luminal-type, and one triple-positive. In addition, another new POU2F3-positive tumor with a triple-negative phenotype was found in daily practice. All non-neoplastic breast tissues contained POU2F3-positive cells, irrespective of BRCA1 status. The scRNA-seq reanalysis confirmed POU2F3-expressing epithelial cells (3.3% of all epithelial cells) and the 17% that co-expressed the other two tuft cell-related markers (SOX9/AVIL or SOX9/GFI1B), which suggested they were bona fide tuft cells. Of note, SOX9 is also known as the “master regulator” of TNBCs. CONCLUSIONS: POU2F3 expression defines small subsets in various breast cancer subtypes, which can be accompanied by DCIS. The mechanistic relationship between POU2F3 and SOX9 in the breast warrants further analysis to enhance our understanding of normal breast physiology and to clarify the significance of the tuft cell-like phenotype for TNBCs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10949-5. BioMed Central 2023-05-13 /pmc/articles/PMC10183142/ /pubmed/37179317 http://dx.doi.org/10.1186/s12885-023-10949-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yamada, Yosuke
Simon, Ronald
Iwane, Kosuke
Nakanishi, Yuki
Takeuchi, Yasuhide
Yoshizawa, Akihiko
Takada, Masahiro
Toi, Masakazu
Haga, Hironori
Marx, Alexander
Sauter, Guido
An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9
title An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9
title_full An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9
title_fullStr An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9
title_full_unstemmed An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9
title_short An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9
title_sort exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of sox9
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10183142/
https://www.ncbi.nlm.nih.gov/pubmed/37179317
http://dx.doi.org/10.1186/s12885-023-10949-5
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