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Updated: Nov 8, 2025
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
The impact of damage-associated molecules released from canine tumor cells on gene expression in macrophages
Shotaro Eto1,2, Hideyuki Yanai2, Sho Hangai2
1Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Abstract:
Dying or damaged cells that are not completely eradicated by the immune system release their intracellular components in the extracellular space. Aberrant exposure of the damage-associated molecules to the immune system is often associated with inflammation and cancer pathogenesis. Thus, elucidating the role of damage-associated molecules in inducing sterile immune responses is crucial. In this study, we show that prostaglandin E2 (PGE2) is produced in the supernatants from several types of canine necrotic tumor cell lines. Inhibition of PGE2 production by indomethacin, a potent inhibitor of cyclooxygenase (COX) enzymes, induces the expression of tumor necrosis factor (Tnf) mRNA in the necrotic tumor cell supernatants. These results comply with the previous observations reported in mouse cell lines. Furthermore, comprehensive ribonucleic acid-sequencing (RNA-seq) analysis revealed that three categories of genes were induced by the damage-associated molecules: (i) a group of PGE2-inducible genes, (ii) genes that promote inflammation and are suppressed by PGE2, and (iii) a group of genes not suppressed by PGE2. Collectively, our findings reveal the hitherto unknown immune regulatory system by PGE2 and damage-associated molecules, which may have clinical implications in inflammation and cancer.
Insights
Damage-associated molecules from dying cells can trigger inflammation and cancer. This study reveals prostaglandin E2 (PGE2) regulates these sterile immune responses, offering potential clinical insights.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Dying cells release intracellular components, potentially triggering sterile immune responses.
- Aberrant exposure to damage-associated molecules is linked to inflammation and cancer.
- Understanding these molecules' role in immune induction is critical.
Purpose of the Study:
- To investigate the role of prostaglandin E2 (PGE2) in regulating immune responses to damage-associated molecules.
- To elucidate the gene expression changes induced by damage-associated molecules in canine necrotic tumor cells.
Main Methods:
- Analysis of supernatants from canine necrotic tumor cell lines.
- Inhibition of PGE2 production using indomethacin (a cyclooxygenase inhibitor).
- Ribonucleic acid-sequencing (RNA-seq) to analyze gene expression patterns.
Main Results:
- Prostaglandin E2 (PGE2) was detected in canine necrotic tumor cell supernatants.
- Inhibition of PGE2 induced tumor necrosis factor (Tnf) mRNA expression.
- RNA-seq identified PGE2-inducible genes, inflammation-promoting genes suppressed by PGE2, and other induced genes.
Conclusions:
- PGE2 plays a significant role in regulating sterile immune responses to damage-associated molecules.
- A novel immune regulatory system involving PGE2 and damage-associated molecules has been identified.
- Findings suggest potential clinical implications for managing inflammation and cancer.
