Tmod-21. defining the growth factor niche that supports gbm initiation

It has been challenging to fully understand the initiation and progression of Glioblastoma Multiforme (GBM), as the early events in tumour development cannot be readily discerned. Although previous work has hypothesized that genetic alterations, such as chromosome 7 gain and chromosome 10 loss, are critical and conserved during tumour initiation in all GBMs, the functional roles of these events have not been characterized. We have developed a murine model which allows us to study the early stages of GBM initiation in vitro and interrogate the role of specific molecular events at different stages of tumour development. This model combines overexpression of platelet-derived growth factor-AA (PDGF-AA) with inactivation of the tumour suppressor protein, p53 (TP53); two genetic alterations which are alone sufficient to induce gliomagenesis. This model provides us with an opportunity to explore the roles of growth factor signaling and p53 in regulating brain tumour initiation in a murine system. In this model, cells from the subventricular zone (SVZ) of p53 null mice are cultured in PDGF-AA for several months. After this time the cells transform; becoming growth factor independent and tumorigenic. We have found that p53 null SVZ cells struggle to survive when cultured in PDGF-AA, but eventually adapt and resume proliferating. In contrast, p53 wildtype cells fail to recover and proliferate when cultured in PDGF-AA. However, when p53 wildtype cells are cultured in PDGF-AA with an add...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MODELS Source Type: research