Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203

Min Zhou; Jionghuang Chen; Liangjing Zhou; Wenchao Chen; Guoping Ding; Liping Cao

doi:10.1016/j.cellimm.2014.09.004

Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203

Cell Immunol. 2014 Nov-Dec;292(1-2):65-9. doi: 10.1016/j.cellimm.2014.09.004. Epub 2014 Sep 28.

Authors

Min Zhou¹, Jionghuang Chen¹, Liangjing Zhou¹, Wenchao Chen¹, Guoping Ding¹, Liping Cao²

Affiliations

¹ Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
² Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. Electronic address: zjulipingcao@163.com.

PMID: 25290620
DOI: 10.1016/j.cellimm.2014.09.004

Abstract

MicroRNAs (miRNAs) are aberrant in many human tumors which can be transferred to immune cells by tumor-derived exosomes. Dendritic cells (DCs) play an important role in activation of immune response. However, the effect of tumor-derived exosomes on toll-like receptor (TLR) in DCs remains unclear. We investigated the influence of pancreatic cancer derived exosomes on TLR4, and downstream cytokines via miR-203. Our results showed that miR-203 expressed in panc-1 cells and exosomes, and upregulated in exosomes-treated DCs. TLR4 decreased after treatment of exosomes and miR-203 mimics, while increased in exosomes-treated DCs by miR-203 inhibitors. But the mRNA level of TLR4 was not significantly different between DCs and exosomes-treated DCs. Tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) also decreased under treatment of exosomes and miR-203 mimics, both of which increased in exosomes-treated DCs by miR-203 inhibitors. Collectively, pancreatic cancer derived exosomes downregulate TLR4 and downstream cytokines in DCs via miR-203.

Keywords: Dendritic cells; Exosomes; MicroRNAs; Pancreatic cancer; Toll-like receptor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Dendritic Cells / immunology*
Exosomes / immunology*
Gene Expression Regulation, Neoplastic
Humans
Interleukin-12 / biosynthesis
Interleukin-12 / immunology
MicroRNAs / genetics
MicroRNAs / immunology*
Pancreatic Neoplasms / genetics
Pancreatic Neoplasms / immunology*
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / immunology*
Tumor Necrosis Factor-alpha / biosynthesis
Tumor Necrosis Factor-alpha / immunology

Substances

MIRN203 microRNA, human
MicroRNAs
TLR4 protein, human
Toll-Like Receptor 4
Tumor Necrosis Factor-alpha
Interleukin-12