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Clonal analysis of the effect of TGF-beta on the apoptosis-inducing activity of normal cells
G Picht1, N Hundertmark, C P Schmitt
1Abteilung Virologie, Universität Freiburg, Germany.
Abstract:
We have recently described induction of apoptosis in transformed fibroblasts by transforming growth factor type beta (TGF-beta)-treated normal fibroblasts, which leads to the specific elimination of transformed cells. Here we investigate whether the ability to eliminate transformed cells is the property of a specialized subpopulation of normal fibroblasts or whether all cells within the population are able to respond to exogenous TGF-beta by induction of elimination of transformed cells. Clonal analysis of the eliminative capacity of normal fibroblasts showed that all cells are able to induce elimination after addition of optimal concentrations of exogenous TGF-beta. In the absence of exogenously added TGF-beta, a minority of clones exhibited complete eliminative activity. Neither the ability nor the inability to perform elimination in the absence of exogenous TGF-beta was a stable characteristic of the respective cell clones. The number of cell clones with the ability to respond to suboptimal concentrations of TGF-beta increased with the passage number of the normal cells, whereas the number of clones inducing apoptosis in the absence of exogenous TGF-beta remained constant.
Insights
Normal fibroblasts eliminate transformed cells via apoptosis. All normal fibroblast cells can induce this elimination when treated with transforming growth factor beta (TGF-beta), regardless of subpopulation.
Area of Science:
- Cell Biology
- Cancer Research
- Apoptosis Induction
Background:
- Normal fibroblasts can induce apoptosis in transformed cells, leading to selective elimination.
- Transforming growth factor beta (TGF-beta) is implicated in this cell elimination process.
Purpose of the Study:
- To determine if specialized fibroblast subpopulations or all cells possess the capacity to eliminate transformed cells.
- To investigate the role of exogenous TGF-beta in mediating this eliminative function.
Main Methods:
- Clonal analysis of normal fibroblast populations.
- Assessment of apoptosis induction in transformed cells.
- Evaluation of cellular response to varying concentrations of TGF-beta.
Main Results:
- All normal fibroblast clones demonstrated the ability to induce elimination of transformed cells upon addition of optimal TGF-beta concentrations.
- A subset of clones showed spontaneous elimination activity without exogenous TGF-beta, but this trait was not stable.
- Responsiveness to suboptimal TGF-beta increased with cell passage number, while spontaneous apoptosis induction remained constant.
Conclusions:
- The capacity to eliminate transformed cells is a property inherent to all normal fibroblasts, inducible by TGF-beta.
- TGF-beta signaling plays a crucial role in mediating fibroblast-dependent elimination of cancer cells.
- Cellular plasticity influences the responsiveness of fibroblasts to TGF-beta and their ability to induce apoptosis.