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Transforming growth factor beta-treated normal fibroblasts eliminate transformed fibroblasts by induction of
J M Jürgensmeier1, C P Schmitt, E Viesel
1Abteilung Virologie, Universität Freiburg, Germany.
Abstract:
Transforming growth factor beta (TGF-beta) induces normal fibroblasts to perform an inhibitory effect directed against transformed cells (P. Höfler, I. Wehrle, and G. Bauer, Int. J. Cancer, 54: 125-130, 1993). Coculture of normal fibroblasts with transformed cells, either resistant to G 418 or expressing Mx antigen detectable by specific immunofluorescence, allowed discrimination between three theoretical mechanisms of inhibition: irreversible inhibition of proliferation; reversion to the nontransformed phenotype; or elimination of transformed cells. Our data demonstrate that normal fibroblasts treated with TGF-beta are able to eliminate transformed cells by induction of apoptosis. Sensitivity against TGF-beta-induced elimination seems to be a general feature of in vitro-transformed cell lines. TGF-beta-induced elimination of transformed fibroblasts by their untransformed counterparts is proposed as a potential potent control point in carcinogenesis, which may lead to the suppression of transformed cells.
Insights
Transforming growth factor beta (TGF-beta) triggers normal fibroblasts to eliminate cancer cells through apoptosis. This TGF-beta-induced elimination of transformed cells by normal fibroblasts suggests a potential mechanism for controlling cancer development.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Normal fibroblasts can inhibit transformed cells.
- Transforming growth factor beta (TGF-beta) is implicated in cellular interactions.
- Mechanisms of fibroblast-mediated inhibition of transformed cells require clarification.
Purpose of the Study:
- To investigate the mechanism by which TGF-beta-treated normal fibroblasts inhibit transformed cells.
- To determine if TGF-beta induces apoptosis in transformed cells.
- To assess the generalizability of TGF-beta-induced elimination in vitro-transformed cell lines.
Main Methods:
- Coculture of normal fibroblasts with transformed cells (G 418 resistant or Mx antigen positive).
- Treatment of normal fibroblasts with TGF-beta.
- Assessment of transformed cell proliferation, phenotype, and viability.
- Immunofluorescence detection of Mx antigen.
Main Results:
- Normal fibroblasts treated with TGF-beta eliminate transformed cells.
- The elimination mechanism involves the induction of apoptosis in transformed cells.
- Sensitivity to TGF-beta-induced elimination is a common characteristic of in vitro-transformed cell lines.
Conclusions:
- TGF-beta-treated normal fibroblasts induce apoptosis in transformed cells, leading to their elimination.
- This process represents a potential endogenous mechanism for suppressing transformed cells.
- TGF-beta-mediated elimination of transformed cells by normal fibroblasts may serve as a crucial control point in carcinogenesis.