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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: Micallef, Peter, Wu, Yanling, Bauzá-Thorbrügge, Marco, Chanclón, Belén, Vujičić, Milica, Peris, Eduard, Ek, C. Joakim, Wernstedt Asterholm, Ingrid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585035/
https://www.ncbi.nlm.nih.gov/pubmed/34769312
http://dx.doi.org/10.3390/ijms222111881
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author Micallef, Peter
Wu, Yanling
Bauzá-Thorbrügge, Marco
Chanclón, Belén
Vujičić, Milica
Peris, Eduard
Ek, C. Joakim
Wernstedt Asterholm, Ingrid
author_facet Micallef, Peter
Wu, Yanling
Bauzá-Thorbrügge, Marco
Chanclón, Belén
Vujičić, Milica
Peris, Eduard
Ek, C. Joakim
Wernstedt Asterholm, Ingrid
author_sort Micallef, Peter
collection PubMed
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.
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spelling pubmed-85850352021-11-12 Adipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth Micallef, Peter Wu, Yanling Bauzá-Thorbrügge, Marco Chanclón, Belén Vujičić, Milica Peris, Eduard Ek, C. Joakim Wernstedt Asterholm, Ingrid Int J Mol Sci Article 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. MDPI 2021-11-02 /pmc/articles/PMC8585035/ /pubmed/34769312 http://dx.doi.org/10.3390/ijms222111881 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Micallef, Peter
Wu, Yanling
Bauzá-Thorbrügge, Marco
Chanclón, Belén
Vujičić, Milica
Peris, Eduard
Ek, C. Joakim
Wernstedt Asterholm, Ingrid
Adipose Tissue—Breast Cancer Crosstalk Leads to Increased Tumor Lipogenesis Associated with Enhanced Tumor Growth
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585035/
https://www.ncbi.nlm.nih.gov/pubmed/34769312
http://dx.doi.org/10.3390/ijms222111881
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