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

Journal of Immunology Research
Kuang YoulinGou Xin

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. The...Continue Reading

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Citations

Sep 24, 2019·Molecular Medicine Reports·Qing ZhouXue-Fei Tian
Dec 5, 2020·Biology·Federica FinettiLorenza Trabalzini
Jun 7, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shan ZhuJingtao Chen
May 1, 2021·Seminars in Cell & Developmental Biology·Saife N LoneMuzafar A Macha
Aug 14, 2021·Frontiers in Oncology·Natalia ScagliaGiorgia Zadra

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Methods Mentioned

BETA
FACS
Transfection
flow cytometry
Xenograft

Software Mentioned

Quantity One

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