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Breast Adipocyte Co-culture Increases the Expression of Pro-angiogenic Factors in Macrophages

Obese individuals with breast cancer have a poorer prognosis and higher risk of metastatic disease vs. non-obese patients. Adipose tissue in obese individuals is characterized by an enhanced macrophage infiltration, creating a microenvironment that favors tumor progression. Here, we demonstrate a ro...

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Autores principales: Yadav, Nalini V. S., Barcikowski, Arthur, Uehana, Yuko, Jacobs, Aaron T., Connelly, Linda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154118/
https://www.ncbi.nlm.nih.gov/pubmed/32318345
http://dx.doi.org/10.3389/fonc.2020.00454
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author Yadav, Nalini V. S.
Barcikowski, Arthur
Uehana, Yuko
Jacobs, Aaron T.
Connelly, Linda
author_facet Yadav, Nalini V. S.
Barcikowski, Arthur
Uehana, Yuko
Jacobs, Aaron T.
Connelly, Linda
author_sort Yadav, Nalini V. S.
collection PubMed
description Obese individuals with breast cancer have a poorer prognosis and higher risk of metastatic disease vs. non-obese patients. Adipose tissue in obese individuals is characterized by an enhanced macrophage infiltration, creating a microenvironment that favors tumor progression. Here, we demonstrate a role for adipocyte-macrophage interactions in the regulation of angiogenesis. Co-culture of THP-1 macrophages with human breast adipocytes led to increased expression of the pro-angiogenic growth factor, vascular endothelial growth factor A (VEGFA). Several adipocyte-derived proteins including leptin, insulin, IL-6, and TNF-α were each capable of increasing VEGFA expression in THP-1 macrophages, identifying these as possible mediators of the changes that were observed with co-culture. Furthermore, analysis of THP-1 culture media by antibody array revealed that THP-1 secrete several other pro-angiogenic signals in response to adipocyte co-culture, including interleukin 8 (IL-8), matrix metalloproteinase 9 (MMP9), pentraxin 3 (PTX3), and serpin E1 (plasminogen activator inhibitor 1, PAI1) after co-culture with human adipocytes. We used an in vitro endothelial tube formation assay with human vascular endothelial cells to evaluate the effects of THP-1 culture media on angiogenesis. Here, culture media from THP-1 cells previously exposed to human adipocytes stimulated endothelial tube formation more significantly than THP-1 cells cultured alone. In summary, we find that adipocyte co-culture stimulates the expression of pro-angiogenic mediators in macrophages and has pro-angiogenic effects in vitro, thus representing a possible mechanism for the enhanced risk of breast cancer progression in obese individuals.
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spelling pubmed-71541182020-04-21 Breast Adipocyte Co-culture Increases the Expression of Pro-angiogenic Factors in Macrophages Yadav, Nalini V. S. Barcikowski, Arthur Uehana, Yuko Jacobs, Aaron T. Connelly, Linda Front Oncol Oncology Obese individuals with breast cancer have a poorer prognosis and higher risk of metastatic disease vs. non-obese patients. Adipose tissue in obese individuals is characterized by an enhanced macrophage infiltration, creating a microenvironment that favors tumor progression. Here, we demonstrate a role for adipocyte-macrophage interactions in the regulation of angiogenesis. Co-culture of THP-1 macrophages with human breast adipocytes led to increased expression of the pro-angiogenic growth factor, vascular endothelial growth factor A (VEGFA). Several adipocyte-derived proteins including leptin, insulin, IL-6, and TNF-α were each capable of increasing VEGFA expression in THP-1 macrophages, identifying these as possible mediators of the changes that were observed with co-culture. Furthermore, analysis of THP-1 culture media by antibody array revealed that THP-1 secrete several other pro-angiogenic signals in response to adipocyte co-culture, including interleukin 8 (IL-8), matrix metalloproteinase 9 (MMP9), pentraxin 3 (PTX3), and serpin E1 (plasminogen activator inhibitor 1, PAI1) after co-culture with human adipocytes. We used an in vitro endothelial tube formation assay with human vascular endothelial cells to evaluate the effects of THP-1 culture media on angiogenesis. Here, culture media from THP-1 cells previously exposed to human adipocytes stimulated endothelial tube formation more significantly than THP-1 cells cultured alone. In summary, we find that adipocyte co-culture stimulates the expression of pro-angiogenic mediators in macrophages and has pro-angiogenic effects in vitro, thus representing a possible mechanism for the enhanced risk of breast cancer progression in obese individuals. Frontiers Media S.A. 2020-04-07 /pmc/articles/PMC7154118/ /pubmed/32318345 http://dx.doi.org/10.3389/fonc.2020.00454 Text en Copyright © 2020 Yadav, Barcikowski, Uehana, Jacobs and Connelly. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Yadav, Nalini V. S.
Barcikowski, Arthur
Uehana, Yuko
Jacobs, Aaron T.
Connelly, Linda
Breast Adipocyte Co-culture Increases the Expression of Pro-angiogenic Factors in Macrophages
title Breast Adipocyte Co-culture Increases the Expression of Pro-angiogenic Factors in Macrophages
title_full Breast Adipocyte Co-culture Increases the Expression of Pro-angiogenic Factors in Macrophages
title_fullStr Breast Adipocyte Co-culture Increases the Expression of Pro-angiogenic Factors in Macrophages
title_full_unstemmed Breast Adipocyte Co-culture Increases the Expression of Pro-angiogenic Factors in Macrophages
title_short Breast Adipocyte Co-culture Increases the Expression of Pro-angiogenic Factors in Macrophages
title_sort breast adipocyte co-culture increases the expression of pro-angiogenic factors in macrophages
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154118/
https://www.ncbi.nlm.nih.gov/pubmed/32318345
http://dx.doi.org/10.3389/fonc.2020.00454
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