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Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin

Obesity, a recognized risk factor for breast cancer in postmenopausal women, is associated with higher mortality rates regardless of menopausal status, which could in part be explained by therapeutic escape. Indeed, adipose microenvironment has been described to influence the efficiency of chemo- an...

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Autores principales: Delort, Laetitia, Bougaret, Lauriane, Cholet, Juliette, Vermerie, Marion, Billard, Hermine, Decombat, Caroline, Bourgne, Céline, Berger, Marc, Dumontet, Charles, Caldefie-Chezet, Florence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950701/
https://www.ncbi.nlm.nih.gov/pubmed/31756890
http://dx.doi.org/10.3390/nu11122839
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author Delort, Laetitia
Bougaret, Lauriane
Cholet, Juliette
Vermerie, Marion
Billard, Hermine
Decombat, Caroline
Bourgne, Céline
Berger, Marc
Dumontet, Charles
Caldefie-Chezet, Florence
author_facet Delort, Laetitia
Bougaret, Lauriane
Cholet, Juliette
Vermerie, Marion
Billard, Hermine
Decombat, Caroline
Bourgne, Céline
Berger, Marc
Dumontet, Charles
Caldefie-Chezet, Florence
author_sort Delort, Laetitia
collection PubMed
description Obesity, a recognized risk factor for breast cancer in postmenopausal women, is associated with higher mortality rates regardless of menopausal status, which could in part be explained by therapeutic escape. Indeed, adipose microenvironment has been described to influence the efficiency of chemo- and hormonal therapies. Residual cancer stem cells could also have a key role in this process. To understand the mechanisms involved in the reduced efficacy of hormonal therapy on breast cancer cells in the presence of adipose secretome, human adipose stem cells (hMAD cell line) differentiated into mature adipocytes were co-cultured with mammary breast cancer cells and treated with hormonal therapies (tamoxifen, fulvestrant). Proliferation and apoptosis were measured (fluorescence test, impedancemetry, cytometry) and the gene expression profile was evaluated. Cancer stem cells were isolated from mammospheres made from MCF-7. The impact of chemo- and hormonal therapies and leptin was evaluated in this population. hMAD-differentiated mature adipocytes and their secretions were able to increase mammary cancer cell proliferation and to suppress the antiproliferative effect of tamoxifen, confirming previous data and validating our model. Apoptosis and cell cycle did not seem to be involved in this process. The evaluation of gene expression profiles suggested that STAT3 could be a possible target. On the contrary, leptin did not seem to be involved. The study of isolated cancer stem cells revealed that their proliferation was stimulated in the presence of anticancer therapies (tamoxifen, fulvestrant, doxorubicine) and leptin. Our study confirmed the role of adipocytes and their secretome, but above all, the role of communication between adipose and cancer cells in interfering with the efficiency of hormonal therapy. Among the pathophysiological mechanisms involved, leptin does not seem to interfere with the estrogenic pathway but seems to promote the proliferation of cancer stem cells.
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spelling pubmed-69507012020-01-16 Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin Delort, Laetitia Bougaret, Lauriane Cholet, Juliette Vermerie, Marion Billard, Hermine Decombat, Caroline Bourgne, Céline Berger, Marc Dumontet, Charles Caldefie-Chezet, Florence Nutrients Article Obesity, a recognized risk factor for breast cancer in postmenopausal women, is associated with higher mortality rates regardless of menopausal status, which could in part be explained by therapeutic escape. Indeed, adipose microenvironment has been described to influence the efficiency of chemo- and hormonal therapies. Residual cancer stem cells could also have a key role in this process. To understand the mechanisms involved in the reduced efficacy of hormonal therapy on breast cancer cells in the presence of adipose secretome, human adipose stem cells (hMAD cell line) differentiated into mature adipocytes were co-cultured with mammary breast cancer cells and treated with hormonal therapies (tamoxifen, fulvestrant). Proliferation and apoptosis were measured (fluorescence test, impedancemetry, cytometry) and the gene expression profile was evaluated. Cancer stem cells were isolated from mammospheres made from MCF-7. The impact of chemo- and hormonal therapies and leptin was evaluated in this population. hMAD-differentiated mature adipocytes and their secretions were able to increase mammary cancer cell proliferation and to suppress the antiproliferative effect of tamoxifen, confirming previous data and validating our model. Apoptosis and cell cycle did not seem to be involved in this process. The evaluation of gene expression profiles suggested that STAT3 could be a possible target. On the contrary, leptin did not seem to be involved. The study of isolated cancer stem cells revealed that their proliferation was stimulated in the presence of anticancer therapies (tamoxifen, fulvestrant, doxorubicine) and leptin. Our study confirmed the role of adipocytes and their secretome, but above all, the role of communication between adipose and cancer cells in interfering with the efficiency of hormonal therapy. Among the pathophysiological mechanisms involved, leptin does not seem to interfere with the estrogenic pathway but seems to promote the proliferation of cancer stem cells. MDPI 2019-11-20 /pmc/articles/PMC6950701/ /pubmed/31756890 http://dx.doi.org/10.3390/nu11122839 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Delort, Laetitia
Bougaret, Lauriane
Cholet, Juliette
Vermerie, Marion
Billard, Hermine
Decombat, Caroline
Bourgne, Céline
Berger, Marc
Dumontet, Charles
Caldefie-Chezet, Florence
Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin
title Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin
title_full Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin
title_fullStr Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin
title_full_unstemmed Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin
title_short Hormonal Therapy Resistance and Breast Cancer: Involvement of Adipocytes and Leptin
title_sort hormonal therapy resistance and breast cancer: involvement of adipocytes and leptin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950701/
https://www.ncbi.nlm.nih.gov/pubmed/31756890
http://dx.doi.org/10.3390/nu11122839
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