TMIC-43. STROMAL REACTIVATION BY GLIOBLASTOMA CELLS PROMOTES TUMOR GROWTH AND TRANSCRIPTIONAL REPROGRAMMING OF ASTROCYTES

Le résumé fourni par la source

Glioblastoma is a highly heterogeneous disease, characterized by high invasion, florid angiogenesis and poor prognosis. Data from recent years introduces the microenvironmental involvement in glioma biology. Still the involvement of astrocytes in Gliomas is not completely understood. We have previously shown that tumor associated astrocytes isolated from mouse models of primary glioblastomas undergo a change in gene expression profile compared to control astrocytes. Suggesting an epigenetic shift of the stroma of glioblastoma. Furthermore, co-implantation of different ratios of normal human astrocytes with a glioma cell line revealed a shortened survival in correlation with increased number of normal astrocytes, suggesting an astrocytic involvement in glioma growth. The aim of the study is therefore to increase our knowledge of how the astrocytic involvement facilitates tumor growth. We have created an in vitro co-culture 3D model system to understand the shift in transcriptional factors of human astrocytes when cultured with primary glioblastoma cell lines created from patient biopsies as well as commercially available cell lines. Using FACS sorting we have been able to separate DsRed normal human astrocytes and glioma cells from the 3D model, thus being able to investigate changes in the two cell types on a transcriptional level using qRT-PCR and microarray. We have found an upregulation in astrocytes of the reprogramming factors SOX2 and POU3F2. This led to establishment of a normal human astrocyte cell line with dual knock down of SOX2 and POU3F2. Current work aims to further understand the expression profile of human glioblastoma-associated astrocytes, and map key factors contributing to the growth promoting effect astrocytes have on glioblastoma cells, potentially leading to a new therapeutic targets.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.