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Prostaglandin E(2) Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway

Migration and homing of dendritic cells (DCs) to lymphoid organs are quite crucial for T cell-induced immune response against tumor. However, tumor microenvironment can make some tumor cells escape immune response by impairing DC migration. Prostaglandin E(2) (PGE(2)) plays important roles in initia...

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Detalles Bibliográficos
Autores principales: Youlin, Kuang, Weiyang, He, Simin, Liang, Xin, Gou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904800/
https://www.ncbi.nlm.nih.gov/pubmed/29850633
http://dx.doi.org/10.1155/2018/5808962
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author Youlin, Kuang
Weiyang, He
Simin, Liang
Xin, Gou
author_facet Youlin, Kuang
Weiyang, He
Simin, Liang
Xin, Gou
author_sort Youlin, Kuang
collection PubMed
description Migration and homing of dendritic cells (DCs) to lymphoid organs are quite crucial for T cell-induced immune response against tumor. However, tumor microenvironment can make some tumor cells escape immune response by impairing DC migration. Prostaglandin E(2) (PGE(2)) plays important roles in initiating and terminating inflammatory responses. In this study, we investigated whether PGE(2) could inhibit murine prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration. We found that murine prostate cancer cell line RM-1-conditioned medium impaired chemotactic movement of marrow-derived DCs and splenic cDCs toward CC chemokine receptor-7 (CCR7) ligand CCL19 in vitro and migration to draining lymph gland in vivo. Meanwhile, it also induced LXRα activation and CCR7 inhibition on maturing DCs. However, the treatment of PGE(2) rescued this impairment of DC migration with upregulation of CCR7 and inhibition of LXRα. Further, it was observed that PGE(2) also increased MMP9 expression and activated Notch1 signaling on DCs. In RM-1-bearing mouse model, PGE(2) treatment was identified to inhibit tumor growth and induce more tumor-infiltrating T cells and CD11c dendritic cells in tumor sites. Therefore, our findings may demonstrate a new perspective for therapeutic interventions on prostate cancer immunoescape.
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spelling pubmed-59048002018-05-30 Prostaglandin E(2) Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway Youlin, Kuang Weiyang, He Simin, Liang Xin, Gou J Immunol Res Research Article Migration and homing of dendritic cells (DCs) to lymphoid organs are quite crucial for T cell-induced immune response against tumor. However, tumor microenvironment can make some tumor cells escape immune response by impairing DC migration. Prostaglandin E(2) (PGE(2)) plays important roles in initiating and terminating inflammatory responses. In this study, we investigated whether PGE(2) could inhibit murine prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration. We found that murine prostate cancer cell line RM-1-conditioned medium impaired chemotactic movement of marrow-derived DCs and splenic cDCs toward CC chemokine receptor-7 (CCR7) ligand CCL19 in vitro and migration to draining lymph gland in vivo. Meanwhile, it also induced LXRα activation and CCR7 inhibition on maturing DCs. However, the treatment of PGE(2) rescued this impairment of DC migration with upregulation of CCR7 and inhibition of LXRα. Further, it was observed that PGE(2) also increased MMP9 expression and activated Notch1 signaling on DCs. In RM-1-bearing mouse model, PGE(2) treatment was identified to inhibit tumor growth and induce more tumor-infiltrating T cells and CD11c dendritic cells in tumor sites. Therefore, our findings may demonstrate a new perspective for therapeutic interventions on prostate cancer immunoescape. Hindawi 2018-04-04 /pmc/articles/PMC5904800/ /pubmed/29850633 http://dx.doi.org/10.1155/2018/5808962 Text en Copyright © 2018 Kuang Youlin et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Youlin, Kuang
Weiyang, He
Simin, Liang
Xin, Gou
Prostaglandin E(2) Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway
title Prostaglandin E(2) Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway
title_full Prostaglandin E(2) Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway
title_fullStr Prostaglandin E(2) Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway
title_full_unstemmed Prostaglandin E(2) Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway
title_short Prostaglandin E(2) Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway
title_sort prostaglandin e(2) inhibits prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration through lxrα/ccr7 pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904800/
https://www.ncbi.nlm.nih.gov/pubmed/29850633
http://dx.doi.org/10.1155/2018/5808962
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