期刊
JOURNAL OF NEURO-ONCOLOGY
卷 85, 期 2, 页码 133-148出版社
SPRINGER
DOI: 10.1007/s11060-007-9400-9
关键词
glioma; dog; U251; U87; CNS-1; GL26
资金
- FIC NIH HHS [R03 TW006273-01A1, R03 TW006273, 1 RO3 TW006273-01] Funding Source: Medline
- NINDS NIH HHS [U01 NS052465, R21 NS047298, R21 NS054143-01A2, U01 NS052465-01A2, 1 RO1 NS 054193.01, R01 NS042893-01A1, R01 NS054193, R01 NS054193-01A1, U54 NS045309-010005, U54 NS045309, 1UO1 NS052465.01, R01 NS044556-01, F32 NS058156, 1R21-NS054143.01, R01 NS042893, R21 NS047298-01, R21 NS054143, 1F32 NS058156.01, 1R01 NS44556.01, NS445561, R01 NS044556] Funding Source: Medline
Although rodent glioblastoma (GBM) models have been used for over 30 years, the extent to which they recapitulate the characteristics encountered in human GBMs remains controversial. We studied the histopathological features of dog GBM and human xenograft GBM models in immune-deficient mice (U251 and U87 GBM in nude Balb/c), and syngeneic GBMs in immune-competent rodents (GL26 cells in C57BL/6 mice, CNS-1 cells in Lewis rats). All GBMs studied exhibited neovascularization, pleomorphism, vimentin immunoreactivity, and infiltration of T-cells and macrophages. All the tumors showed necrosis and hemorrhages, except the U87 human xenograft, in which the most salient feature was its profuse neovascularization. The tumors differed in the expression of astrocytic intermediate filaments: human and dog GBMs, as well as U251 xenografts expressed glial fibrillary acidic protein (GFAP) and vimentin, while the U87 xenograft and the syngeneic rodent GBMs were GFAP(-) and vimentin(+). Also, only dog GBMs exhibited endothelial proliferation, a key feature that was absent in the murine models. In all spontaneous and implanted GBMs we found histopathological features compatible with tumor invasion into the non-neoplastic brain parenchyma. Our data indicate that murine models of GBM appear to recapitulate several of the human GBM histopathological features and, considering their reproducibility and availability, they constitute a valuable in vivo system for preclinical studies. Importantly, our results indicate that dog GBM emerges as an attractive animal model for testing novel therapies in a spontaneous tumor in the context of a larger brain.
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