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Published on: October 30, 2013
In vitro tumoral progression of human bladder carcinoma: role for TGFbeta
Pierre Champelovier1, Michèle El Atifi, Frédéric Mantel
1Laboratoires de Cytologie, Centre Hospitalier Universitaire de Grenoble, Departement d'Anatomie et Cytologie Pathologique, Hôpital A. Michallon, BP 217, 38043 Grenoble cedex 09, France. pchampelovier@chu-grenoble.fr
Objective:
Investigating whether extracellular factors are possible actors in tumoral progression in bladder carcinoma.
Methods:
RT112/G2 bladder tumour cells were grown in presence of TGFbeta and analysed by immunological and cDNA microarray techniques.
Results:
TGFbeta inhibited cell proliferation, reduced TNFalpha- and IFNgamma-induced apoptosis by decreasing TNFalpha-RI and IFNgamma-R antigen expression. It also inhibited cleaved caspase 8 and 9 expression, decreased E-cadherin, and increased BclxL and cyclooxygenase-2 expression. The cDNA microarray approach showed that TGFbeta up-regulated the expression of genes with defined roles in tumoral progression sometimes associated with poor outcome in bladder cancer.
Conclusion:
These results suggest that a part of the bladder tumoral progression process may be related to the action of exogenous TGFbeta confirming the possible role for the microenvironment.
Insights
Transforming growth factor beta (TGF-β) influences bladder cancer progression by altering cell apoptosis and gene expression. Exogenous TGF-β may play a role in tumor development, highlighting the microenvironment
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Extracellular factors are increasingly recognized for their role in cancer development.
- The tumor microenvironment significantly impacts cancer progression.
- Understanding these interactions is crucial for identifying new therapeutic targets in bladder carcinoma.
Purpose of the Study:
- To investigate the role of extracellular factors, specifically Transforming Growth Factor beta (TGF-β), in the progression of bladder carcinoma.
- To elucidate the molecular mechanisms by which TGF-β affects bladder tumor cells.
Main Methods:
- RT112/G2 bladder tumor cells were cultured in the presence of TGF-β.
- Immunological techniques were employed to analyze cellular responses.
- cDNA microarray analysis was used to assess gene expression changes.
Main Results:
- TGF-β inhibited cell proliferation and reduced tumor necrosis factor-alpha (TNFα)- and interferon-gamma (IFNγ)-induced apoptosis.
- TGF-β decreased the expression of TNFα receptor I (TNFα-RI) and IFNγ receptor (IFNγ-R) and inhibited cleaved caspase 8 and 9.
- TGF-β modulated the expression of key genes involved in tumoral progression, including decreased E-cadherin and increased BclxL and cyclooxygenase-2.
Conclusions:
- Exogenous TGF-β influences bladder tumor cell behavior, including proliferation and apoptosis.
- TGF-β upregulates genes associated with tumor progression and potentially poor outcomes in bladder cancer.
- These findings support the role of the tumor microenvironment, specifically TGF-β, in bladder carcinoma progression.
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