Tmod-25. modeling adult proneural and mesenchymal glioblastoma using rcas/t-va technology

Glioblastoma (GBM) is the most common and aggressive malignant glioma, characterized by genetic heterogeneity, resistance to treatment, and dismal prognosis. The bulk of research in GBM biology utilizes passaged cell lines and xenograft models that may neglect some aspects of the tumor-stroma interactions, particularly the actions of the immune system. Additionally, the standard of care neglects the four subtypes that have been identified through analysis of the Cancer Genome Atlas. In order to advance exact research into GBM tumorigenesis, progression and treatment, we utilized RCAS/t-va technology to develop mouse models of adult proneural and mesenchymal GBM. The proneural GBM model was generated by overexpression of platelet-derived growth factor (PDGFB) in adult Ntv-a; Ink4a-Arf -/- ;Pten fl/fl mice. The mesenchymal GBM model was generated by co-injecting RCAS-shNf1, RCAS-shp53 and RCAS-Cre into sub ventricular zone of adult Ntv-a; Ink4a-Arf -/- ;Pten fl/fl mice. Both models display near to 100 % tumor formation. Comparison of these two models has demonstrated marked differences in the tumor microenvironment. Most notably, the mesenchymal subtype displays a significantly higher proportion of activated macrophage and microglia within the tumor as measured by immunohistochemical staining for macrophage markers Iba1 and CD68. Moreover, CD31 staining shows significantly higher vessel coverage and larger average vessel size in the proneural subtype. The data generated...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MODELS Source Type: research