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Published on: June 16, 2018
Spontaneous regression of lung metastasis in the absence of tumor necrosis factor receptor p55
Yoshiharu Tomita1, Xiaoqin Yang, Yuko Ishida
1Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Abstract:
In order to clarify the roles of tumor necrosis factor (TNF)-alpha in lung metastasis, we injected Renca cells intravenously into TNF receptor p55-deficient (TNF-Rp55 KO) and wild-type (WT) mice. Microscopic and macroscopic metastasis foci appeared in lungs at 7 and 14 days after the tumor injection, respectively. Moreover, metastasis foci expanded at similar rates in both WT and TNF-Rp55 KO mice until 21 days, and lungs were occupied with metastasis foci. However, later than 21 days after the injection, metastasis foci spontaneously regressed in TNF-Rp55 KO mice, whereas WT mice exhibited a progressive growth of metastasis foci. Moreover, metastasis foci remained reduced sizes in TNF-Rp55 KO mice even at 26 days, when all WT mice died with lungs filled with metastasis foci. Later than 21 days after the tumor injection, the number of apoptotic tumor cells was increased in TNF-Rp55 KO mice. In contrast, neovascularization was less evident in TNF-Rp55 KO than WT mice, with depressed hepatocyte growth factor (HGF) gene in TNF-Rp55 KO mice at 21 days after the tumor injection. Thus, TNF-Rp55-mediated signals can maintain tumor neovascularization at least partly by inducing HGF expression, and eventually support lung metastasis process.
Insights
Tumor necrosis factor receptor p55 (TNF-Rp55) deficiency halts lung metastasis progression by reducing tumor neovascularization and increasing cancer cell apoptosis. This suggests TNF-Rp55 signaling supports metastasis growth.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor necrosis factor-alpha (TNF-α) is implicated in various biological processes, including inflammation and cancer.
- The specific role of TNF-α signaling pathways, particularly through its p55 receptor (TNF-Rp55), in lung metastasis remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of TNF receptor p55 (TNF-Rp55) in the process of lung metastasis.
- To determine how TNF-Rp55 signaling influences tumor growth, apoptosis, and neovascularization in a lung metastasis model.
Main Methods:
- Intravenous injection of Renca cells into wild-type (WT) and TNF-Rp55 knockout (TNF-Rp55 KO) mice.
- Monitoring and quantification of lung metastasis foci at various time points (7, 14, 21, and 26 days post-injection).
- Assessment of tumor cell apoptosis, neovascularization, and hepatocyte growth factor (HGF) gene expression in lung tissues.
Main Results:
- While initial metastasis growth was similar, spontaneous regression of lung metastasis foci occurred later than 21 days in TNF-Rp55 KO mice, unlike progressive growth in WT mice.
- TNF-Rp55 KO mice showed increased tumor cell apoptosis and reduced neovascularization compared to WT mice.
- Hepatocyte growth factor (HGF) gene expression was depressed in TNF-Rp55 KO mice, suggesting a mechanism for reduced neovascularization.
Conclusions:
- TNF-Rp55-mediated signals are crucial for maintaining tumor neovascularization, partly through the induction of HGF expression.
- Blocking TNF-Rp55 signaling can inhibit lung metastasis progression by promoting tumor cell apoptosis and reducing neovascularization.
- Targeting the TNF-Rp55 pathway may represent a therapeutic strategy to combat lung metastasis.
