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


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.


CONCLUSIONS
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.
Dutour
A
A
Department of Medical Biochemistry School of Medicine, University of Limoges, 2 rue Dr Raymond Marcland, 87042 Limoges, France.
Rabinovich-Chable
H
H
Kaletta
C
C
Michaelis
U
U
Fiorenza
F
F
Sturtz
F
F
Rigaud
M
M
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000008:administration & dosage / Q000235:genetics; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D008081:Liposomes / Q000008:administration & dosage; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy; D012516:Osteosarcoma / Q000098:blood supply* / Q000235:genetics / Q000628:therapy*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D019210:Troponin I / Q000235:genetics*
D018076:DNA, Complementary; D008081:Liposomes; D019210:Troponin I