TY - JOUR T1 - Is Troponin I Gene Therapy Effective for Osteosarcoma Treatment? Study on a Human-like Orthotopic Rat Model JF - Anticancer Research JO - Anticancer Res SP - 3977 LP - 3982 VL - 24 IS - 6 AU - A. DUTOUR AU - H. RABINOVICH-CHABLE AU - C. KALETTA AU - U. MICHAELIS AU - F. FIORENZA AU - F. STURTZ AU - M. RIGAUD Y1 - 2004/11/01 UR - http://ar.iiarjournals.org/content/24/6/3977.abstract N2 - Background: An anti-angiogenesis strategy has been widely recognized as a viable approach to fight cancer and more and more anti-angiogenic factors are continually being identified. Among them, the muscular isoform of Troponin I (TnI) has been described as being a powerful anti-angiogenic agent in vitro as well as in vivo. We investigated the therapeutic efficacy of TnI gene therapy in a human-like orthotopic rat osteosarcoma model. Materials and Methods: In this tumor model, we evaluated whether the administration of the secreted TnI coding sequence complexed to cationic liposomes (named TnITag cDNA/lCLP) could induce a delay in tumor growth and reduce tumor vasculature. Results: Although TnI specifically inhibited endothelial cell growth in vitro, we were not able to demonstrate any therapeutic efficacy of TnI in the transplantable osteosarcoma model. Conclusion: This lack of efficacy probably resulted from the rapid degradation of recombinant TnI by matrix metalloproteinases, especially MMP2, which are present in large amounts in tumors. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -