Immunohistopathological and neuroimaging characterization of murine orthotopic xenograft models of glioblastoma multiforme recapitulating the most salient features of human disease
Articolo
Data di Pubblicazione:
2009
Citazione:
Immunohistopathological and neuroimaging characterization of murine orthotopic xenograft models of glioblastoma multiforme recapitulating the most salient features of human disease / E. Radaelli, R. Ceruti, V. Patton, M. Russo, A. Degrassi, V. Croci, F. Caprera, G. Stortini, E. Scanziani, E. Pesenti, R. Alzani. - In: HISTOLOGY AND HISTOPATHOLOGY. - ISSN 0213-3911. - 24:7(2009 Jul), pp. 879-891.
Abstract:
Tumorigenesis in human glioblastoma multiforme (GBM) is driven by several genetic
abnormalities with disruption of important molecular pathways, such as
p53/MDM2/p14ARF and EGFR/PTEN/Akt/mTOR. The malignant progression of human GBM is
also primarily associated with a peculiar multistep pathophysiological process
characterized by intratumoral ischemic necrosis (i.e. pseudopalisading necrosis)
and activation of the hypoxia-inducible factor (HIF)-1alpha pathway with
consequent peritumoral microvascular proliferation and infiltrative behaviour.
Predictable preclinical animal models of GBM should recapitulate the main
pathobiological hallmarks of the human disease. In this study we describe two
murine orthotopic xenograft models using U87MG and U251 human cell lines. Ten
Balb/c nude male mice were orthotopically implanted with either U87MG (5 mice) or
U251 (5 mice) cell lines. Intracranial tumor growth was monitored through
Magnetic Resonance Imaging (MRI). Immunohistopathological examination of the
whole cranium was performed 30 days after implantation. U251 orthotopic
xenografts recapitulated the salient pathobiological features described for human
GBM, including invasive behaviour, wide areas of pseudopalisading necrosis,
florid peripheral angiogenesis, GFAP and vimentin expression, nonfunctional p53
expression, striking active-caspase-3 and HIF-1alpha expression along
pseudopalisades. U87MG orthotopic xenografts proved to be very dissimilar from
human GBM, showing expansile growth, occasional necrotic foci without
pseudopalisades, intratumoral lacunar pattern of angiogenesis, lack of GFAP
expression, functional p53 expression and inconsistent HIF-1alpha expression.
Expression of pAkt was upregulated in both models. The results obtained suggest
that the U251 orthotopic model may be proposed as a predictive and reliable tool
in preclinical studies since it recapitulates the most salient pathobiological
features reported for human GBM.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Glioblastoma multiforme ; hypoxia-inducible factor-1 ; mouse model ; pseudopalisading necrosis
Elenco autori:
E. Radaelli, R. Ceruti, V. Patton, M. Russo, A. Degrassi, V. Croci, F. Caprera, G. Stortini, E. Scanziani, E. Pesenti, R. Alzani
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