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Mechanism of the cytotoxic effect of tumor necrosis factor
Abstract:
The mechanism of murine tumor necrosis factor (TNF) cytotoxicity against tumor cell lines (L929, HeLa, K562) was investigated. Electron microscopic observation revealed that most of the organellas of L929 cells incubated with partially purified murine TNF underwent almost complete lysis with no drastic disruption of the cytoplasmic membrane, while injection of the TNF into the cytoplasm or nuclei of L929 cells caused no apparent morphological change or growth inhibition. Preincubation of the TNF with tumor cells (L929, HeLa, K562) resulted in a decrease in cytotoxic activity which was proportional to their susceptibility to TNF, thus indicating their absorption of TNF. The susceptibility of L929 tumor cells to TNF was apparently suppressed by treatment with proteases, suggesting the existence of protease-sensitive recognition sites for TNF on the tumor cell.
Insights
Murine tumor necrosis factor (TNF) causes tumor cell lysis by targeting organelles without disrupting the cell membrane. Tumor cells absorb TNF, and protease-sensitive sites on their surface mediate this interaction.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Tumor necrosis factor (TNF) is a cytokine with known cytotoxic effects on tumor cells.
- The precise mechanism by which TNF induces tumor cell death remains an area of active investigation.
Purpose of the Study:
- To elucidate the mechanism of murine TNF-induced cytotoxicity against various tumor cell lines.
- To identify the cellular components and surface interactions involved in TNF-mediated cell death.
Main Methods:
- Electron microscopy was used to observe morphological changes in tumor cells treated with TNF.
- Tumor cells were preincubated with TNF to assess TNF absorption and its effect on cytotoxicity.
- Protease treatment was employed to investigate the role of cell surface receptors.
Main Results:
- Electron microscopy revealed lysis of organelles within L929 cells treated with TNF, without significant plasma membrane disruption.
- Direct injection of TNF into L929 cell cytoplasm or nuclei did not induce morphological changes or growth inhibition.
- Cytotoxic activity decreased proportionally to TNF absorption by tumor cells (L929, HeLa, K562).
- Protease treatment reduced the susceptibility of L929 cells to TNF, indicating protease-sensitive recognition sites.
Conclusions:
- Murine TNF-induced cytotoxicity involves the lysis of intracellular organelles rather than direct plasma membrane damage.
- Tumor cell surface receptors, sensitive to proteases, play a crucial role in TNF recognition and subsequent cytotoxicity.