Adipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth

We sought to identify therapeutic targets for breast cancer by investigating the metabolic symbiosis between breast cancer and adipose tissue. To this end, we compared orthotopic E0771 breast cancer tumors that were in direct contact with adipose tissue with ectopic E0771 tumors in mice. Orthotopic...

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Autores principales:	Peter Micallef, Yanling Wu, Marco Bauzá-Thorbrügge, Belén Chanclón, Milica Vujičić, Eduard Peris, C. Joakim Ek, Ingrid Wernstedt Asterholm
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	E0771 luminal B breast cancer adipose tissue mouse lipolysis Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/efcb9a24ab954ef5b1ffc5d9bba20aba
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spelling	oai:doaj.org-article:efcb9a24ab954ef5b1ffc5d9bba20aba2021-11-11T17:18:09ZAdipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth10.3390/ijms2221118811422-00671661-6596https://doaj.org/article/efcb9a24ab954ef5b1ffc5d9bba20aba2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11881https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067We sought to identify therapeutic targets for breast cancer by investigating the metabolic symbiosis between breast cancer and adipose tissue. To this end, we compared orthotopic E0771 breast cancer tumors that were in direct contact with adipose tissue with ectopic E0771 tumors in mice. Orthotopic tumors grew faster and displayed increased de novo lipogenesis compared to ectopic tumors. Adipocytes release large amounts of lactate, and we found that both lactate pretreatment and adipose tissue co-culture augmented de novo lipogenesis in E0771 cells. Continuous treatment with the selective FASN inhibitor Fasnall dose-dependently decreased the E0771 viability in vitro. However, daily Fasnall injections were effective only in 50% of the tumors, while the other 50% displayed accelerated growth. These opposing effects of Fasnall in vivo was recapitulated in vitro; intermittent Fasnall treatment increased the E0771 viability at lower concentrations and suppressed the viability at higher concentrations. In conclusion, our data suggest that adipose tissue enhances tumor growth by stimulating lipogenesis. However, targeting lipogenesis alone can be deleterious. To circumvent the tumor’s ability to adapt to treatment, we therefore believe that it is necessary to apply an aggressive treatment, preferably targeting several metabolic pathways simultaneously, together with conventional therapy.Peter MicallefYanling WuMarco Bauzá-ThorbrüggeBelén ChanclónMilica VujičićEduard PerisC. Joakim EkIngrid Wernstedt AsterholmMDPI AGarticleE0771luminal Bbreast canceradipose tissuemouselipolysisBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11881, p 11881 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	E0771 luminal B breast cancer adipose tissue mouse lipolysis Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	E0771 luminal B breast cancer adipose tissue mouse lipolysis Biology (General) QH301-705.5 Chemistry QD1-999 Peter Micallef Yanling Wu Marco Bauzá-Thorbrügge Belén Chanclón Milica Vujičić Eduard Peris C. Joakim Ek Ingrid Wernstedt Asterholm Adipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth
description	We sought to identify therapeutic targets for breast cancer by investigating the metabolic symbiosis between breast cancer and adipose tissue. To this end, we compared orthotopic E0771 breast cancer tumors that were in direct contact with adipose tissue with ectopic E0771 tumors in mice. Orthotopic tumors grew faster and displayed increased de novo lipogenesis compared to ectopic tumors. Adipocytes release large amounts of lactate, and we found that both lactate pretreatment and adipose tissue co-culture augmented de novo lipogenesis in E0771 cells. Continuous treatment with the selective FASN inhibitor Fasnall dose-dependently decreased the E0771 viability in vitro. However, daily Fasnall injections were effective only in 50% of the tumors, while the other 50% displayed accelerated growth. These opposing effects of Fasnall in vivo was recapitulated in vitro; intermittent Fasnall treatment increased the E0771 viability at lower concentrations and suppressed the viability at higher concentrations. In conclusion, our data suggest that adipose tissue enhances tumor growth by stimulating lipogenesis. However, targeting lipogenesis alone can be deleterious. To circumvent the tumor’s ability to adapt to treatment, we therefore believe that it is necessary to apply an aggressive treatment, preferably targeting several metabolic pathways simultaneously, together with conventional therapy.
format	article
author	Peter Micallef Yanling Wu Marco Bauzá-Thorbrügge Belén Chanclón Milica Vujičić Eduard Peris C. Joakim Ek Ingrid Wernstedt Asterholm
author_facet	Peter Micallef Yanling Wu Marco Bauzá-Thorbrügge Belén Chanclón Milica Vujičić Eduard Peris C. Joakim Ek Ingrid Wernstedt Asterholm
author_sort	Peter Micallef
title	Adipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth
title_short	Adipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth
title_full	Adipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth
title_fullStr	Adipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth
title_full_unstemmed	Adipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth
title_sort	adipose tissue—breast cancer crosstalk leads to increased tumor lipogenesis associated with enhanced tumor growth
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/efcb9a24ab954ef5b1ffc5d9bba20aba
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Adipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth

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