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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Taylor & Francis Group
2021
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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) |
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adipocytes breast cancer lipolysis fatty acids inflammation treatment resistance Diseases of the endocrine glands. Clinical endocrinology RC648-665 Cytology QH573-671 Physiology QP1-981 |
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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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