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[Study on tumor necrosis factor receptor of human gastric cancer cells]
Objective:
To explore the relationship between the number of tumor necrosis factor receptors (TNFR) and the degree of differentiation of gastric cancer cells, and the relationship between the number of TNFR and the cytotoxicity of tumor necrosis factor mutant (TNF-m).
Methods:
With 125I-TNF-m, the radio-ligand binding assay was used to detect the TNFR on three gastric cancer cell lines (MKN28, SGC7901 MKN45) with from high to low degrees of differentiation. MTT colorimetric method was used to study the cytotoxicity of TNF-m on the three gastric cancer cell lines in vitro.
Results:
The number of TNFR of the three gestric cancer cells was 9.8 x 10(-12) nmol, 5.6 x 10(-12) nmol and 3.2 x 10(-12) nmol per cell respectively it differed significent from each other (P < 0.05) but the dissociation constant was basically the same. The rate of TNF-m internalization of the three gastric cancer cells was nearly the same and temperature dependent. The half-life of TNFR was about 90 mins. The ratio of membrane receptors to cytoplasm receptors was about 0.5. The maximum killing rate of TNF-m was 86%, 60% and 34% for MKN28, SGC7901, MKN45 cells, respectively, which were significantly different (P < 0.05). Killing rate of TNF-m to these cells at 39 degrees C was higher than at 37 degrees C.
Conclusions:
The number of TNFR on the surface of gastric cancer cells was associated with the degree of differentiation of gastric cancer cells. The cytotoxicity of TNF-m was related to the number of TNFR and the rate of internalization of TNF-m.
Insights
Gastric cancer cell differentiation correlates with tumor necrosis factor receptor (TNFR) numbers. Higher TNFR levels on gastric cancer cells increase sensitivity to tumor necrosis factor mutant (TNF-m) cytotoxicity.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Context:
- Gastric cancer exhibits variable differentiation, impacting treatment response.
- Tumor Necrosis Factor Receptors (TNFR) play a role in cellular signaling and apoptosis.
- Understanding receptor-ligand interactions is crucial for targeted therapies.
Purpose:
- To investigate the association between the quantity of tumor necrosis factor receptors (TNFR) and the differentiation status of gastric cancer cells.
- To determine the relationship between TNFR levels and the cytotoxic effects of a tumor necrosis factor mutant (TNF-m).
Summary:
- Radio-ligand binding assays revealed significant differences in TNFR numbers across three gastric cancer cell lines (MKN28, SGC7901, MKN45) with varying differentiation.
- In vitro cytotoxicity assays demonstrated that TNF-m's killing rate on these cell lines (86%, 60%, 34% respectively) was significantly correlated with their respective TNFR expression levels.
- TNF-m internalization rates were similar across cell lines but temperature-dependent, with higher efficacy at 39°C compared to 37°C.
Impact:
- Establishes a quantitative link between gastric cancer cell differentiation and TNFR expression.
- Suggests that TNFR levels and TNF-m internalization rates are key determinants of TNF-m's efficacy in gastric cancer.
- Provides a basis for exploring TNF-m as a targeted therapy for gastric cancer, potentially stratified by TNFR expression.