Abstract
Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.
Highlights
Gliomas are the most common forms of primary human brain tumors, and they are often classified into four clinical grades
Another major disadvantage of the orthotopic models using xenografted human glioblastoma multiforme (GBM) cell lines in rodents is that genetic alterations present in the original tumor are not often maintained, especially the overexpression or amplification of the epidermal growth factor receptor (EGFR) gene that is present in approximately 40%–50% of human GBM is typically not preserved in GBM cell lines and xenografts derived thereof [6, 15,16,17]
The heterotopic or orthotopic models from human GBM cell lines do not recapitulate an extremely important aspect of tumor invasion and EGFR gene overexpression, which has somewhat limited its application in clinically relevant researches
Summary
Gliomas are the most common forms of primary human brain tumors, and they are often classified into four clinical grades. In the orthotopic setting, established human GBM cell lines generally fail to demonstrate the diffusely infiltrative pattern of growth that is typical of human GBM [6]; instead, human GBM cell lines tend to form solid masses at the site of injection, which compress rather than invade the surrounding brain parenchyma [12,13,14] Another major disadvantage of the orthotopic models using xenografted human GBM cell lines in rodents is that genetic alterations present in the original tumor are not often maintained, especially the overexpression or amplification of the EGFR gene that is present in approximately 40%–50% of human GBM is typically not preserved in GBM cell lines and xenografts derived thereof [6, 15,16,17]. The heterotopic or orthotopic models from human GBM cell lines do not recapitulate an extremely important aspect of tumor invasion and EGFR gene overexpression, which has somewhat limited its application in clinically relevant researches
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