382 Human Cancer Cells Migrating in Human Brain: Directly from the Operating Room

INTRODUCTION: Glioblastoma (GBM) is a highly invasive tumor for which there is no effective treatment. Migratory cells invade the healthy parenchyma, evading treatment and promoting recurrence. The role microenvironment plays in the invasion of GBM has been commonly studied with reductionist systems that do not recapitulate the cytoarchitecture of the human brain. METHODS: Healthy brain samples were obtained from patients undergoing non-cancer related surgery. Organotypic explants from human brain were prepared and maintained for two weeks. GFP-labeled GBM cells were injected into the organotypic under microscopic visualization. Migration was evaluated via microscopy and immunohistochemistry techniques. Motility was analyzed by a computational method designed for this project. RESULTS: After inoculation, cells migrated successfully into the tissue. After 7 days, immuno-staining demonstrated that GBM cells were located near blood vessels. Approximately 50 ± 20% of cells had migrated to within 10 μm of the vessel (n = 28 regions, 10 tissues). Cells initially migrated with limited directionality sending processes in different directions and upon contact, cells moved faster towards the vessel. After merging, migration speed decreased and continued to decrease with time (p < 0.001). Directionality increased after a process contact with the vessel (p < 0.001) and then returned to the pre-contact directionality once merged (p < 0.001). After perivascular localization, migration was limited along the blood vessels in both directions. The percentage of cells that contact and then continue to migrate along the vessel was 96.8 ± 3.1% while the percentage of cells that migrate to the vessel and leave was 3.2 ± 3.1%. CONCLUSIONS: Our human-tumor-on-human-brain organotypic model serves as a favorable system to study GBM invasion. We confirm that GBM utilizes blood vessels to migrate and found that there is a change in migratory dynamics upon blood vessel contact.