Is troponin I gene therapy effective for osteosarcoma treatment? Study on a human-like orthotopic rat model.

Abstract

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.