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Journal of Immunology Research
Volume 2018, Article ID 5808962, 8 pages
https://doi.org/10.1155/2018/5808962
Research Article

Prostaglandin E2 Inhibits Prostate Cancer Progression by Countervailing Tumor Microenvironment-Induced Impairment of Dendritic Cell Migration through LXRα/CCR7 Pathway

Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

Correspondence should be addressed to Kuang Youlin; moc.361@163lyk

Received 1 December 2017; Revised 11 February 2018; Accepted 20 February 2018; Published 4 April 2018

Academic Editor: Maria Cristina Gagliardi

Copyright © 2018 Kuang Youlin et al. 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.

Abstract

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 E2 (PGE2) plays important roles in initiating and terminating inflammatory responses. In this study, we investigated whether PGE2 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 PGE2 rescued this impairment of DC migration with upregulation of CCR7 and inhibition of LXRα. Further, it was observed that PGE2 also increased MMP9 expression and activated Notch1 signaling on DCs. In RM-1-bearing mouse model, PGE2 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.