Related Experiment Videos
Decrease in lymphokine-activated killer sensitivity of a human renal-cell carcinoma cell line after cytokine
M Yanase1, T Tsukamoto, Y Kumamoto
1Department of Urology, Sapporo Medical University, Japan.
Abstract:
Recent studies have shown that cytokine treatment of tumor cells alters the sensitivity of these cells to lymphokine-activated killer (LAK) cells, depending on the cell line. In this study, we analyzed the decrease in LAK sensitivity of a human renal-cell carcinoma cell line (SMKT-R-3). The LAK sensitivity of SMKT-R-3 was decreased by treatment with a combination of interferon gamma (IFN gamma) and tumor necrosis factor (TNF). However, the cytokine treatment increased the expression of intercellular adhesion molecule-1 (ICAM-1) on the renal-cell carcinoma cell surface. The conjugate-formation assay also confirmed a slight increase in the binding rate of LAK cells to the renal-cell carcinoma cells. When actinomycin D (a protein synthesis inhibitor) was added to the culture medium prior to treatment with IFN gamma and TNF, the LAK sensitivity of SMKT-R-3 recovered to the level demonstrated by the cells that had not received any cytokine treatment. These results suggest that the effect of cytokines in reducing LAK sensitivity of SMKT-R-3 is mediated by protein synthesis occurring when LAK cells are bound to SMKT-R-3 cells.
Insights
Cytokine treatment decreased the sensitivity of renal-cell carcinoma cells to lymphokine-activated killer (LAK) cells. This reduction in LAK sensitivity was linked to protein synthesis, suggesting a novel therapeutic target.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Cytokine therapy can modulate tumor cell sensitivity to immune effector cells like lymphokine-activated killer (LAK) cells.
- The specific mechanisms underlying these modulations vary significantly between different tumor cell lines.
Purpose of the Study:
- To investigate the impact of cytokine treatment on the LAK cell sensitivity of a human renal-cell carcinoma cell line (SMKT-R-3).
- To elucidate the molecular mechanisms responsible for altered LAK sensitivity following cytokine exposure.
Main Methods:
- Treatment of SMKT-R-3 cells with a combination of interferon gamma (IFN-γ) and tumor necrosis factor (TNF).
- Assessment of LAK cell sensitivity and expression of intercellular adhesion molecule-1 (ICAM-1).
- Evaluation of LAK sensitivity in the presence of actinomycin D, a protein synthesis inhibitor.
Main Results:
- Cytokine treatment (IFN-γ and TNF) decreased the LAK sensitivity of SMKT-R-3 cells.
- Cytokine treatment led to increased expression of ICAM-1 on the tumor cell surface.
- Inhibition of protein synthesis with actinomycin D restored LAK sensitivity to baseline levels.
Conclusions:
- The observed decrease in LAK sensitivity of renal-cell carcinoma cells by cytokine treatment is mediated by protein synthesis.
- These findings suggest that protein synthesis occurring during LAK cell interaction with tumor cells plays a crucial role in modulating immune response.