Towards gene therapy for spontaneous brain glioma in dogs. Optimization of adenoviral vector mediated expression in the canine brain in vivo, and in canine glioma cells in vitro

CANDOLFI; PLUHAR; KROEGER; PUNTEL; CURTIN; BARCIA; MUHAMMAD; XIONG; LIU; MONDKAR; KUOY; KANG; MCNIEL; FREESE; OHLFEST; MOORE; PALMER; NG; YOUNG; LOWENSTEIN; CASTRO

JOURNAL OF NEURO-ONCOLOGY.

SPRINGER

Año: 2007 p. 245 - 258

0167-594X

Although rodent glioblastoma (GBM) modelshave been used for over 30 years, the extent to which theyrecapitulate the characteristics encountered in humanGBMs remains controversial. We studied the histopathologicalfeatures of dog GBM and human xenograft GBMmodels in immune-deficient mice (U251 and U87 GBM innude Balb/c), and syngeneic GBMs in immune-competentrodents (GL26 cells in C57BL/6 mice, CNS-1 cells inLewis rats). All GBMs studied exhibited neovascularization,pleomorphism, vimentin immunoreactivity, andinfiltration of T-cells and macrophages. All the tumorsshowed necrosis and hemorrhages, except the U87 humanxenograft, in which the most salient feature was its profuseneovascularization. The tumors differed in the expressionof astrocytic intermediate filaments: human and dogGBMs, as well as U251 xenografts expressed glial fibrillaryacidic protein (GFAP) and vimentin, while the U87xenograft and the syngeneic rodent GBMs were GFAP–and vimentin+. Also, only dog GBMs exhibited endothelialproliferation, a key feature that was absent in the murinemodels. In all spontaneous and implanted GBMs we foundhistopathological features compatible with tumor invasioninto the non-neoplastic brain parenchyma. Our data indicatethat murine models of GBM appear to recapitulateseveral of the human GBM histopathological featuresand, considering their reproducibility and availability, theyconstitute a valuable in vivo system for preclinical studies.Importantly, our results indicate that dog GBM emerges asan attractive animal model for testing novel therapies in aspontaneous tumor in the context of a larger brain.