Abstract 1574: The role of human cerebrospinal fluid in glioblastoma malignancy

Glioblastoma (GBM), also known as grade IV astrocytoma, is the most common and devastating primary cancer of the central nervous system in adults. Despite the most advanced therapeutic strategies combining surgery, chemotherapy, and radiation, survival expectancy of GBM patients averages 14 months, with a recurrence rate of almost 100%. Remarkably, tumor location has great implications in the prognosis of GBM. Approximately 50-60% of GBM tumors infiltrates or contacts the subventricular zone (SVZ). These patients have significantly worse outcomes, in terms of median overall survival, time to progression and reoccurrence. The reason for the worse prognosis of SVZ-infiltrating tumors is unknown. The SVZ is the largest neurogenic niche in the adult brain, here the differentiation and migration of SVZ cells is regulated by direct contact with the cerebrospinal fluid (CSF). We suggest that CSF contribute to enhance GBM malignant characteristics in SVZ-infiltrating tumors. This study evaluated the impact of CSF exposure on GBM cells proliferation, migration in vitro and in vivo, as well as changes in gene expression profile. We demonstrated that CSF affects the malignancy of GBM cells by increasing their ability to proliferate and migrate. GBM cells stimulated with cancer CSF, non-cancer CSF, or control conditions at different time points (24-72 hrs) were evaluated for viability (by Alamar Blue assay) and proliferation rate (Ki67+ immunostaining), as well as for migratory capabilities (by means of transwell assay and time-lapse microscopy). We recapitulated these CSF effects in vivo using an in vivo model in which both female and male nude mice were implanted with GBM cells in suspension with human cancer or non-cancer CSF in an hydrogel as vehicle (n=8 mice per group). Tumor growth was followed via IVIS imaging and then studied by measuring tumor area on HE 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1574.