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Updated: May 27, 2026
08:19
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Tumor necrosis factor receptor 1 functions as a tumor suppressor
Fengqi Chang1, Michelle R Lacey, Mostafa Bouljihad
1Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Summary
Tumor necrosis factor receptor 1 (TNFR1) loss increases colitis-associated cancer risk. TNFR1 acts as a tumor suppressor by controlling epithelial proliferation and beta-catenin activation, not apoptosis.
Area of Science:
- Gastroenterology
- Oncology
- Immunology
Background:
- Tumor necrosis factor (TNF) plays a role in inflammatory bowel disease and cancer.
- TNF receptor 1 (TNFR1) signaling is protective in experimental colitis.
- The interplay between inflammation and tumorigenesis requires further elucidation.
Purpose of the Study:
- To investigate the role of TNF and TNFR1 in colitis-associated carcinogenesis.
- To determine if TNFR1 loss increases the risk of colon cancer development.
- To explore the mechanisms by which TNFR1 influences neoplastic transformation.
Main Methods:
- Utilized three murine models of tumorigenesis.
- Compared wild-type (WT), TNFR1 knockout (R1KO), and TNF knockout (TNFKO) mice.
- Assessed disease severity, inflammation, apoptosis, epithelial proliferation, and beta-catenin activation.
Main Results:
- R1KO mice exhibited more severe colitis and increased frequency/earlier onset of neoplastic lesions.
- TNFR1 deficiency led to heightened epithelial proliferation and earlier, more intense activated beta-catenin expression.
- TNFR1 loss did not affect apoptosis but modulated Wnt signaling.
Conclusions:
- TNFR1 functions as a tumor suppressor in colitis-associated carcinogenesis.
- TNFR1 exerts its tumor-suppressive effect by modulating beta-catenin activation and epithelial proliferation.
- These findings highlight TNFR1's critical role in balancing inflammation and tumorigenesis in the colon.
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