Role of cellular origin for tumorigenicity of glioma-derived cancer initiating cells
Time period: 2011-01-01 to 2013-12-31
Project leader: Lene Uhrbom
Funder: Ragnar Söderberg Foundation
Type of award: Project grant
Total fundning: 1 083 237 SEK
Malignant glioma is the most common and severe form of primary brain tumor in adults. Notably, the origin of glioma is still undefined but assumed to be a glial stem or progenitor cell. Recently cancer initiating cells (CICs) were identified in gliomas. CICs are a subpopulation of cells with increased resistance to chemotherapy and radiation believed to be uniquely responsible for maintenance, progression and recurrence of glioma. We propose to analyse the role of cellular origin in glioma for survival and malignant phenotype of CICs. We will use a well-characterized experimental model in which the target cell for gliomagenesis can be specified. Cultured CICs of different cellular origin will be analysed with regard to quantity, phenotype and global gene expression and data related to survival and malignancy of the primary tumor to try to identify molecular markers and pathways defining different subgroups based on cellular origin. The same analyses will be conducted on freshly cultured human glioma CICs and data sets compared to investigate if mouse data can be used to clinically stratify glioma patients and identify novel markers and pathways in human CICs. We have preliminary data supporting clear differences in survival and quality of CICs of different cellular origin and believe that the project has high potential to generate important new knowledge for the understanding of basic glioma biology and contribute to better prognosis and treatment of glioma patients.