Investigating Glioblastoma Invasiveness in a Mouse Model of Neurovascular Deficiency

Abstract

Glioblastoma is the most common malignant brain tumour and has the lowest 5-year survival rate among CNS tumours at only 4.9%. A key driver of glioblastoma development is the vasculature, which it relies on heavily due to the lack of energy storage in brain tissue. Glioblastoma uses several different methods of angiogenesis to address the metabolic needs of tumour growth. Given how reliant this type of cancer is on its angiogenic and metabolic activity, it would be intriguing to see how glioblastoma progression changes when these factors are perturbed. 16p11.2 deletion syndrome is a copy number variation which has been associated with many different developmental conditions. While most of the work associated with this deletion syndrome is associated with autism spectrum disorder, we are interested in the cerebrovascular and metabolic alterations associated with the deletion. Our lab has demonstrated that 16p11.2-haploinsufficient (16p11.2df/+) mice have pertinent neurovascular and metabolic deficits, which make this mouse model a candidate for studies involving glioblastoma. Using the Wiesner model of glioblastoma induction, we sought to assess whether glioblastoma progression would be hindered in 16p11.2df/+ mice compared to WT mice. After assessing the subventricular zone for differences in morphology and relevant cell populations, we used the Wiesner model in 16p11.2df/+ mice and successfully induced both wild-type and 16p11.2df/+ mice. Within these groups, 16p11.2df/+ mice were found to have reduced GFP+ cell expression, reduced bulk tumour tissue area, and altered morphology of the tumour vasculature. Taken altogether, our findings suggest that genes within the 16p11.2 locus may contribute to glioblastoma-associated vascular remodeling.