98%
921
2 minutes
20
Metastasis is a major cause of poor prognosis of pancreatic cancer. Exosomes (Exos) regulate cancer progression by modulating macrophage polarization. This study aimed to investigate the effects of cancer-associated fibroblast (CAF)-released Exos on macrophage polarization in pancreatic cancer and the molecular mechanisms. THP-1 cells or xenografted tumor mice were treated with Exos from CAFs, and macrophage polarization was analyzed using quantitative real-time PCR (qPCR) and flow cytometry. THP-1 cells were cocultured with BXPC-3 cells, and metastasis was analyzed using Transwell assay and scratch test. Exosomal PTGS2 was detected using qPCR, and the NOD1 pathway was evaluated using western blot analysis. The results showed that Exos promoted M2-type polarization and inhibited M1-type polarization, and then facilitated pancreatic cancer cell migration, invasion, and epithelial-mesenchymal transition. PTGS2 expression was increased in Exo-treated macrophages, and its knockdown in CAFs facilitated M2 to M1 macrophage polarization. Moreover, Exos promoted the NOD1 pathway via PTGS2, and inhibition of NOD1 reversed the polarization caused by Exos. Additionally, NOD1 was required in M1/M2 polarization in vivo mediated by Exos. In conclusion, CAF-secreted Exos facilitated M2 macrophage polarization by carrying PTGS2 to activate the NOD1 pathway, thereby promoting pancreatic cancer metastasis, providing evidence that CAF-Exos accelerating pancreatic cancer progression.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/jbt.70126 | DOI Listing |
Naunyn Schmiedebergs Arch Pharmacol
September 2025
Department of Gastroenterology, Jinhua Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, Zhejiang, China.
The fourth leading cause of cancer-related fatalities in the USA is pancreatic ductal adenocarcinoma (PDAC), a particularly deadly illness that is resistant to immunotherapy. One of the Main Obstacles in cancer research is developing better treatments for PDAC, which has the lowest 5-year survival rate of any malignancy. Anti-CTLA-4, anti-PD-L1, and anti-PD-1 immune checkpoint blockade medications also have poor results in these patients, which may indicate the presence of other immunosuppressive mechanisms in the pancreatic tumor microenvironment (TME).
View Article and Find Full Text PDFJ Bioenerg Biomembr
September 2025
Department of Vascular, Shanghai TCM-INTEGRATED Hospital, Shanghai, 200082, China.
This study aimed to investigate the therapeutic effects of Sini Decoction on a murine model of peripheral arterial disease (PAD) and to explore its potential mechanisms of action related to mitochondrial autophagy and M1 macrophage polarization. A total of 36 specific-pathogen-free Kunming mice were used to establish a PAD model and were randomly assigned into four groups: the experimental group (EG, administered Sini Decoction via gavage), the control group (CG, administered rapamycin via gavage), the model group (MG, administered 0.9% sodium chloride solution via gavage), and the normal group (NG, administered 0.
View Article and Find Full Text PDFAdv Mater
September 2025
State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Bone defect therapy frequently encounters bacterial infections and chronic inflammation, which impair bone regeneration and threaten implant stability. Iron oxide nanoparticles have attracted attention due to cost-effectiveness, biocompatibility, and metabolic safety. However, iron oxide nanoparticles still struggle to balance low-temperature efficient antibacterial activity, effective immunomodulation, and bone regeneration.
View Article and Find Full Text PDFMol Cell Biol
September 2025
Medical School of Tianjin University, Tianjin, China.
Over the past few decades, liver disease has emerged as one of the leading causes of death worldwide. Liver injury is frequently associated with infections, alcohol consumption, or obesity, which trigger hepatic inflammation and ultimately lead to progressive fibrosis and carcinoma. Although various cell populations contribute to inflammatory and fibrogenic processes in the liver, macrophages serve as a pivotal mediator.
View Article and Find Full Text PDFRegen Biomater
August 2025
College of Textiles & Clothing, Institute of Functional Textiles and Advanced Materials, Qingdao 266071, China.
Bacterial infection in the injured skin may threaten the wound repair and skin regeneration owing to aggravated inflammation. The multifunctional dressings with persistent antibacterial activity and improved anti-inflammatory capability are urgently required. Herein, a type of heterogeneous zinc/catechol-derived resin microspheres (Zn/CFRs) composed of zinc ions (Zn) and zinc oxide (ZnO) nanoparticles was developed to impart the methacrylamide chitosan (CSMA)-oxidized hyaluronic acid (OHA) hydrogel with a persistent Zn release behavior.
View Article and Find Full Text PDF