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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Bibliographic Details
Published in:	Frontiers in oncology Vol. 10; p. 454
Main Authors:	Yadav, Nalini V S, Barcikowski, Arthur, Uehana, Yuko, Jacobs, Aaron T, Connelly, Linda
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 07-04-2020
Subjects:	adipocytes breast macrophages obesity Oncology vascular endothelial growth factor (VEGF) vascular endothelial growth factor (VEGF) macrophages adipocytes breast obesity
Online Access:	Get full text
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Summary:	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 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 , thus representing a possible mechanism for the enhanced risk of breast cancer progression in obese individuals.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Lasse Dahl Ejby Jensen, Linköping University, Sweden Reviewed by: Gabor Csanyi, Augusta University, United States; Monica Montopoli, University of Padova, Italy This article was submitted to Molecular and Cellular Oncology, a section of the journal Frontiers in Oncology
ISSN:	2234-943X 2234-943X
DOI:	10.3389/fonc.2020.00454