Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 133-148 |
| Number of pages | 16 |
| Journal | Journal of Neuro-Oncology |
| Volume | 85 |
| Issue number | 2 |
| DOIs | |
| State | Published - Nov 2007 |
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Keywords
- CNS-1
- Dog
- GL26
- Glioma
- U251
- U87
ASJC Scopus subject areas
- Clinical Neurology
- Cancer Research
- Oncology
- Neuroscience(all)
Cite this
Intracranial glioblastoma models in preclinical neuro-oncology : Neuropathological characterization and tumor progression. / Candolfi, Marianela; Curtin, James F.; Nichols, W. Stephen; Muhammad, A. K M G; King, Gwendalyn D.; Pluhar, G. Elizabeth; McNiel, Elizabeth A.; Ohlfest, John R.; Freese, Andrew B.; Moore, Peter F; Lerner, Jonathan; Lowenstein, Pedro R.; Castro, Maria G.
In: Journal of Neuro-Oncology, Vol. 85, No. 2, 11.2007, p. 133-148.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intracranial glioblastoma models in preclinical neuro-oncology
T2 - Neuropathological characterization and tumor progression
AU - Candolfi, Marianela
AU - Curtin, James F.
AU - Nichols, W. Stephen
AU - Muhammad, A. K M G
AU - King, Gwendalyn D.
AU - Pluhar, G. Elizabeth
AU - McNiel, Elizabeth A.
AU - Ohlfest, John R.
AU - Freese, Andrew B.
AU - Moore, Peter F
AU - Lerner, Jonathan
AU - Lowenstein, Pedro R.
AU - Castro, Maria G.
PY - 2007/11
Y1 - 2007/11
N2 - 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.
AB - 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.
KW - CNS-1
KW - Dog
KW - GL26
KW - Glioma
KW - U251
KW - U87
UR - http://www.scopus.com/inward/record.url?scp=35449004503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35449004503&partnerID=8YFLogxK
U2 - 10.1007/s11060-007-9400-9
DO - 10.1007/s11060-007-9400-9
M3 - Article
C2 - 17874037
AN - SCOPUS:35449004503
VL - 85
SP - 133
EP - 148
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 2
ER -