M2 Macrophage-Derived Exosomes Promote Angiogenesis and Growth of Pancreatic Ductal Adenocarcinoma by Targeting E2F2

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2020 Nov 22

PMID 33221435

Citations 128

Authors

Yuhan Yang

Zengya Guo

Weiwei Chen

Xiaofeng Wang

Meng Cao

Xuan Han

Kundong Zhang

Buwei Teng

Jun Cao

Weidong Wu

Peng Cao

Chen Huang

Zhengjun Qiu

Affiliations

Soon will be listed here.

Abstract

Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive tumors all over the world, has a generally poor prognosis, and its progression is positively correlated with the density of blood vessels. Recently, tumor-associated macrophages (TAMs) were proven to be beneficial for angiogenesis, but their mechanism of action remains unclear. Our study indicated that M2 macrophages were positively correlated with the microvessel density (MVD) of PDAC tissues, and M2 macrophage-derived exosomes (MDEs) could promote the angiogenesis of mouse aortic endothelial cells (MAECs) in vitro. At the same time, the M2 MDEs could also promote the growth of subcutaneous tumors and increase the vascular density of mice. Moreover, we also found that miR-155-5p and miR-221-5p levels in the M2 MDEs were higher than those in M0 MDEs, and they could be transferred into MAECs, as demonstrated by RNA sequencing (RNA-seq) and qPCR analysis. Our data confirmed the interaction between TAMs and the angiogenesis of PDAC by exosomes. Additionally, targeting the exosomal miRNAs derived from TAMs might provide diagnostic and therapeutic strategies for PDAC.

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