Is Interferon γ One Key of Metastatic Potential Increase in Human Bladder Carcinoma?

• Published in: Clinical cancer research 2003-10, Vol.9 (12), p.4562-4569
• Main Authors: CHAMPELOVIER, Pierre, SIMON, Annick, GARREL, Catherine, LEVACHER, Geraldine, PRALORAN, Vincent, SEIGNEURIN, Daniel
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Biomarkers, Tumor - metabolism; Caspases - metabolism; Cell Division - drug effects; Cell Movement - drug effects; Dissemination; Drug Resistance, Neoplasm; Hepatocyte Growth Factor - secretion; Humans; Interferon-gamma - pharmacology; Medical sciences; Signal Transduction; Tumor cell; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - pharmacology; Tumors; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - secondary
• ISSN: 1078-0432; 1557-3265

Purpose: IFN-γ is detected in the urine of bladder cancer patients after intravesical bacillus Calmette Guerin instillation. Because it acts in the anticancer process, we studied its cellular and molecular mechanisms of action on human bladder cancer cell lines. Results: IFN-γ (>5 ng·ml −1 )(>400 IU·ml −1 ) inhibited the growth of bladder cancer cell lines and modified the expression of the tumor-associated markers tissue-type plasminogen activators, Plasminogen activator inhibitor-2, urokinase plasminogen activator receptor, colony-stimulating factor 1, intercellular adhesion molecule 1, and class II MHC. Interestingly, IFN-γ-induced apoptosis of the low-grade bladder cancer cell lines (RT4/G1 and RT112/G2) related to a cleavage of caspases 1, 8, and 9. This process was inhibited by the phosphatidylinositol 3′-kinase inhibitor (LY294002) and the protein synthesis inhibitor (cycloheximide). Moreover, low doses of IFN-γ (