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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8585035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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