Effects of Obesity on the Regulation of Macrophage Population in the Prostate Tumor Microenvironment

Effects of Obesity on the Regulation of Macrophage Population in the Prostate Tumor Microenvironment

Obesity is associated with a greater risk of prostate cancer mortality. However, the mechanisms connecting obesity to the progression of prostate cancer remain unknown. This study determined the impact of obesity on macrophage recruitment and tumor-associated macrophage (TAM) polarization in the pro...

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Bibliographic Details
Published in:Nutrition and cancer Vol. 69; no. 7; pp. 996 - 1002
Main Authors: Galván, G. C., Johnson, C. B., Price, R. S., Liss, M. A., Jolly, C. A., deGraffenried, L. A.
Format: Journal Article
Language:English
Published: United States Taylor & Francis 03-10-2017
Taylor & Francis Ltd
Subjects:
Adipocytes
Animals
Arginase
Cancer
Cell Line, Tumor
Chemokine CCL2 - genetics
Conditioning
Cyclooxygenase 2 - genetics
Cyclooxygenase-2
Dinoprostone - metabolism
Enzyme-linked immunosorbent assay
Epithelial Cells - metabolism
Epithelial Cells - pathology
Gelatinase B
Health risks
Humans
Infiltration
Interleukin 10
Macrophages
Macrophages - metabolism
Macrophages - pathology
Male
Markers
Metastases
Mice, Inbred C57BL
Mice, Obese
Monocyte chemoattractant protein 1
mRNA
Obesity
Obesity - complications
Obesity - pathology
Paracrine Communication
Polarization
Prostaglandin E2
Prostate cancer
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
PTEN Phosphohydrolase - genetics
PTEN Phosphohydrolase - metabolism
PTEN protein
Transforming growth factor-b
Tumor Microenvironment
Tumors
Vascular endothelial growth factor
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Summary:Obesity is associated with a greater risk of prostate cancer mortality. However, the mechanisms connecting obesity to the progression of prostate cancer remain unknown. This study determined the impact of obesity on macrophage recruitment and tumor-associated macrophage (TAM) polarization in the prostate tumor microenvironment, since a high concentration of TAMs in tumors has been linked to progression in prostate cancer. We utilized an in vitro model in which pre-adipocytes, prostate cancer cells, and macrophages were exposed to sera from obese or nonobese men, or conditioned media generated under obese or nonobese conditions. Matrigel invasion chambers were used to assess macrophage recruitment in vitro, and immunohistochemical analysis evaluated recruitment in a PTEN knockout mouse model. qPCR was used to measure mRNA levels of CCL2, COX-2, IL-10, TGF-beta, VEGF-A, arginase-1, and MMP-9. PGE2 production was measured by ELISA. Obesity increased macrophage and TAM recruitment, and increased mRNA levels of TAM markers in macrophages. Similarly, obese conditions increased CCL2 and COX-2 expression, as well as PGE2 levels in prostate cancer cells. COX-2 inhibition resulted in lower expression of obesity-induced TAM markers. Our data suggest that obesity promotes macrophage infiltration into the prostate tumor microenvironment, and induces TAM polarization through the COX-2/PGE2 pathway.
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ISSN:0163-5581
1532-7914
DOI:10.1080/01635581.2017.1359320