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Updated: Jun 28, 2025
Elevated Plus Maze for Mice
Published on: December 22, 2008
TNF receptor 2 knockout mouse had reduced lung cancer growth and schizophrenia-like behavior through a decrease in
In Jun Yeo1, Ji Eun Yu2, Sung-Hyun Kim3
1College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 41566, Republic of Korea.
Abstract:
The relationship between schizophrenia (SCZ) and cancer development remains controversial. Based on the disease-gene association platform, it has been revealed that tumor necrosis factor receptor (TNFR) could be an important mediatory factor in both cancer and SCZ development. TNF-α also increases the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) in the development of SCZ and tumor, but the role of TNFR in mediating the association between the two diseases remains unclear. We studied the vital roles of TNFR2 in the progression of tumor and SCZ-like behavior using A549 lung cancer cell xenografted TNFR2 knockout mice. TNFR2 knockout mice showed significantly decreased tumor size and weight as well as schizophrenia-like behaviors compared to wild-type mice. Consistent with the reduced tumor growth and SCZ-like behaviors, the levels of TrkB and BDNF expression were significantly decreased in the lung tumor tissues and pre-frontal cortex of TNFR2 knockout mice. However, intravenous injection of BDNF (160 μg/kg) to TNFR2 knockout mice for 4 weeks increased tumor growth and SCZ-like behaviors as well as TrkB expression. In in vitro study, significantly decreased cell growth and expression of TrkB and BDNF by siTNFR2 transfection were found in A549 lung cancer cells. However, the addition of BDNF (100 ng/ml) into TNFR2 siRNA transfected A549 lung cancer cells recovered cell growth and the expression of TrkB. These results suggest that TNFR2 could be an important factor in mediating the comorbidity between lung tumor growth and SCZ development through increased TrkB-dependent BDNF levels.
Insights
Tumor necrosis factor receptor 2 (TNFR2) plays a key role in both lung cancer growth and schizophrenia-like behaviors. Targeting TNFR2 may offer a novel therapeutic strategy for these comorbid conditions.
Area of Science:
- Neuroscience
- Oncology
- Immunology
Background:
- The link between schizophrenia (SCZ) and cancer is debated.
- Tumor necrosis factor receptor (TNFR) is implicated in both SCZ and cancer.
- The specific role of TNFR in mediating SCZ and cancer comorbidity is unclear.
Purpose of the Study:
- To investigate the role of TNFR2 in lung cancer progression and SCZ-like behaviors.
- To elucidate the molecular mechanisms underlying the association between TNFR2, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB).
Main Methods:
- Utilized TNFR2 knockout mice xenografted with A549 lung cancer cells.
- Assessed tumor growth, SCZ-like behaviors, and expression levels of BDNF and TrkB.
- Conducted in vitro studies using A549 cells with siTNFR2 transfection and BDNF treatment.
Main Results:
- TNFR2 knockout mice exhibited reduced tumor size, weight, and SCZ-like behaviors.
- TrkB and BDNF levels were decreased in tumors and brain tissue of TNFR2 knockout mice.
- Exogenous BDNF administration restored tumor growth and SCZ-like behaviors in knockout mice, while BDNF addition rescued cell growth and TrkB expression in vitro.
Conclusions:
- TNFR2 is a critical mediator in the comorbidity of lung tumor growth and SCZ development.
- The TNFR2-dependent regulation of BDNF and TrkB signaling pathways is crucial for this association.
