Tumor-associated Macrophages Promote Pancreatic Ductal Adenocarcinoma Progression by Inducing Epithelial-to-mesenchymal Transition

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2021 Jan 11

PMID 33428605

Citations 14

Authors

Cheng Xiong

Youwei Zhu

Meilin Xue

Yongsheng Jiang

Yiming Zhong

Lingxi Jiang

Minmin Shi

Hao Chen

Affiliations

Soon will be listed here.

Abstract

In this study, we investigated the role of tumor-associated macrophages (TAMs) in the progression of pancreatic ductal adenocarcinoma (PDAC). PDAC patients with higher levels of CD68 TAMs exhibited shorter overall survival. In Transwell assays, PDAC cells incubated with TAMs or conditioned media from TAM cells (TAM-CM) showed higher migration and invasion rates than controls. PET/CT scan analysis of orthotopic PDAC model mice revealed greater primary tumor growth and liver metastasis in the TAM-CM treatment group than the controls. H&E staining of liver tissues showed significantly higher numbers of metastatic nodules in the TAM-CM treatment group. Heat inactivation of TAM-CM significantly reduced Transwell migration by PDAC cells, suggesting the involvement of one or more secreted proteins in PDAC progression. Transcriptome sequencing analysis of PDAC cells treated with TAM-CM revealed significant enrichment of transforming growth factor-β (TGF-β) signaling pathway genes. Western blot and qRT-PCR analysis showed that TAM-CM enhanced PDAC migration cells by inducing epithelial-to-mesenchymal transition through the TGF-β-Smad2/3/4-Snail signaling axis. The pro-tumorigenic effects of TAMs or TAM-CM were abolished by TGF-β signaling pathway inhibitors and neutralizing TGF-β antibody. These results demonstrate that TAMs promote PDAC progression through the TGF-β signaling pathway.

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