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Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate

Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MG...

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Autores principales: Huang, Chun-Kai, Chang, Po-Hao, Kuo, Wen-Hung, Chen, Chi-Long, Jeng, Yung-Ming, Chang, King-Jen, Shew, Jin-Yuh, Hu, Chun-Mei, Lee, Wen-Hwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353665/
https://www.ncbi.nlm.nih.gov/pubmed/28281525
http://dx.doi.org/10.1038/ncomms14706
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author Huang, Chun-Kai
Chang, Po-Hao
Kuo, Wen-Hung
Chen, Chi-Long
Jeng, Yung-Ming
Chang, King-Jen
Shew, Jin-Yuh
Hu, Chun-Mei
Lee, Wen-Hwa
author_facet Huang, Chun-Kai
Chang, Po-Hao
Kuo, Wen-Hung
Chen, Chi-Long
Jeng, Yung-Ming
Chang, King-Jen
Shew, Jin-Yuh
Hu, Chun-Mei
Lee, Wen-Hwa
author_sort Huang, Chun-Kai
collection PubMed
description Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MGDAs) promote growth of breast cancer cells that express monocarboxylate transporter 2 (MCT2) both in vitro and in vivo. We show that β-hydroxybutyrate is secreted by MGDAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, β-hydroxybutyrate is sufficient to promote tumorigenesis of a mouse xenograft model of MCT2-expressing breast cancer cells. Mechanistically we observe that upon co-culturing with MGDAs or treatment with β-hydroxybutyrate, breast cancer cells expressing MCT2 increase the global histone H3K9 acetylation and upregulate several tumour-promoting genes. These results suggest that adipocytes promote malignancy of MCT2-expressing breast cancer via β-hydroxybutyrate potentially by inducing the epigenetic upregulation of tumour-promoting genes.
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spelling pubmed-53536652017-04-05 Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate Huang, Chun-Kai Chang, Po-Hao Kuo, Wen-Hung Chen, Chi-Long Jeng, Yung-Ming Chang, King-Jen Shew, Jin-Yuh Hu, Chun-Mei Lee, Wen-Hwa Nat Commun Article Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MGDAs) promote growth of breast cancer cells that express monocarboxylate transporter 2 (MCT2) both in vitro and in vivo. We show that β-hydroxybutyrate is secreted by MGDAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, β-hydroxybutyrate is sufficient to promote tumorigenesis of a mouse xenograft model of MCT2-expressing breast cancer cells. Mechanistically we observe that upon co-culturing with MGDAs or treatment with β-hydroxybutyrate, breast cancer cells expressing MCT2 increase the global histone H3K9 acetylation and upregulate several tumour-promoting genes. These results suggest that adipocytes promote malignancy of MCT2-expressing breast cancer via β-hydroxybutyrate potentially by inducing the epigenetic upregulation of tumour-promoting genes. Nature Publishing Group 2017-03-10 /pmc/articles/PMC5353665/ /pubmed/28281525 http://dx.doi.org/10.1038/ncomms14706 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Huang, Chun-Kai
Chang, Po-Hao
Kuo, Wen-Hung
Chen, Chi-Long
Jeng, Yung-Ming
Chang, King-Jen
Shew, Jin-Yuh
Hu, Chun-Mei
Lee, Wen-Hwa
Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate
title Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate
title_full Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate
title_fullStr Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate
title_full_unstemmed Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate
title_short Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate
title_sort adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353665/
https://www.ncbi.nlm.nih.gov/pubmed/28281525
http://dx.doi.org/10.1038/ncomms14706
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