The paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells

Adipocytes in the breast tumour microenvironment promotes acquired treatment resistance. We used an in vitro adipocyte-conditioned media approach to investigate the direct paracrine effects of adipocyte secretory factors on MDA-MB-231 breast cancer cells treated with doxorubicin to clarify the under...

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Autores principales: Ilze Mentoor, Anna-Mart Engelbrecht, Mari van de Vyver, Paul J. van Jaarsveld, Theo Nell
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Lenguaje:EN
Publicado: Taylor & Francis Group 2021
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Acceso en línea:https://doaj.org/article/a98c646362144cd38b04f51a2ee5f93f
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spelling oai:doaj.org-article:a98c646362144cd38b04f51a2ee5f93f2021-11-26T11:19:49ZThe paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells2162-39452162-397X10.1080/21623945.2021.1979758https://doaj.org/article/a98c646362144cd38b04f51a2ee5f93f2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/21623945.2021.1979758https://doaj.org/toc/2162-3945https://doaj.org/toc/2162-397XAdipocytes in the breast tumour microenvironment promotes acquired treatment resistance. We used an in vitro adipocyte-conditioned media approach to investigate the direct paracrine effects of adipocyte secretory factors on MDA-MB-231 breast cancer cells treated with doxorubicin to clarify the underlying treatment resistance mechanisms. Cell-viability assays, and Western blots were performed to determine alterations in apoptotic, proliferation and lipid metabolism protein markers. Free fatty acids (FFA) and inflammatory markers in the collected treatment-conditioned media were also quantified. Adipocyte secretory factors increased the cell-viability of doxorubicin-treated cells (p < 0.0001), which did not correspond to apoptosis or proliferation pathways. Adipocyte secretory factors increased the protein expression of hormone-sensitive lipase (p < 0.05) in doxorubicin-treated cells. Adipocyte secretory factors increased the utilization of leptin (p < 0.05) and MCP-1 (p < 0.01) proteins and possibly inhibited release of linoleic acid by doxorubicin-treated cells (treatment-conditioned media FFA profiles). Adipocyte secretory factors induced doxorubicin treatment resistance, by increasing the utilization of inflammatory mediators and inhibiting the release of FFA by doxorubicin-treated cells. This further promotes inflammation and lipid metabolic reprogramming (lipid storage) in the tumour microenvironment, which breast cancer cells use to evade the toxic effects induced by doxorubicin and confers to acquired treatment resistance.Ilze MentoorAnna-Mart EngelbrechtMari van de VyverPaul J. van JaarsveldTheo NellTaylor & Francis Grouparticleadipocytesbreast cancerlipolysisfatty acidsinflammationtreatment resistanceDiseases of the endocrine glands. Clinical endocrinologyRC648-665CytologyQH573-671PhysiologyQP1-981ENAdipocyte, Vol 10, Iss 1, Pp 505-523 (2021)
institution DOAJ
collection DOAJ
language EN
topic adipocytes
breast cancer
lipolysis
fatty acids
inflammation
treatment resistance
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
Cytology
QH573-671
Physiology
QP1-981
spellingShingle adipocytes
breast cancer
lipolysis
fatty acids
inflammation
treatment resistance
Diseases of the endocrine glands. Clinical endocrinology
RC648-665
Cytology
QH573-671
Physiology
QP1-981
Ilze Mentoor
Anna-Mart Engelbrecht
Mari van de Vyver
Paul J. van Jaarsveld
Theo Nell
The paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells
description Adipocytes in the breast tumour microenvironment promotes acquired treatment resistance. We used an in vitro adipocyte-conditioned media approach to investigate the direct paracrine effects of adipocyte secretory factors on MDA-MB-231 breast cancer cells treated with doxorubicin to clarify the underlying treatment resistance mechanisms. Cell-viability assays, and Western blots were performed to determine alterations in apoptotic, proliferation and lipid metabolism protein markers. Free fatty acids (FFA) and inflammatory markers in the collected treatment-conditioned media were also quantified. Adipocyte secretory factors increased the cell-viability of doxorubicin-treated cells (p < 0.0001), which did not correspond to apoptosis or proliferation pathways. Adipocyte secretory factors increased the protein expression of hormone-sensitive lipase (p < 0.05) in doxorubicin-treated cells. Adipocyte secretory factors increased the utilization of leptin (p < 0.05) and MCP-1 (p < 0.01) proteins and possibly inhibited release of linoleic acid by doxorubicin-treated cells (treatment-conditioned media FFA profiles). Adipocyte secretory factors induced doxorubicin treatment resistance, by increasing the utilization of inflammatory mediators and inhibiting the release of FFA by doxorubicin-treated cells. This further promotes inflammation and lipid metabolic reprogramming (lipid storage) in the tumour microenvironment, which breast cancer cells use to evade the toxic effects induced by doxorubicin and confers to acquired treatment resistance.
format article
author Ilze Mentoor
Anna-Mart Engelbrecht
Mari van de Vyver
Paul J. van Jaarsveld
Theo Nell
author_facet Ilze Mentoor
Anna-Mart Engelbrecht
Mari van de Vyver
Paul J. van Jaarsveld
Theo Nell
author_sort Ilze Mentoor
title The paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells
title_short The paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells
title_full The paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells
title_fullStr The paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells
title_full_unstemmed The paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells
title_sort paracrine effects of adipocytes on lipid metabolism in doxorubicin-treated triple negative breast cancer cells
publisher Taylor & Francis Group
publishDate 2021
url https://doaj.org/article/a98c646362144cd38b04f51a2ee5f93f
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