Tumor-specific migration routes of xenotransplanted human glioblastoma cells in mouse brain

Abstract

Abstract The migration of neural progenitor cells (NPCs) to their final destination during development follows well-defined pathways. Cells from the highly malignant tumor glioblastoma (GBM) appear to exploit similar routes to invade brain parenchyma. In this report, we have analyzed the migration of GBM cells using three-dimensional high-resolution confocal microscopy in brain tumors derived from eight different human GBM cell lines xenografted in immunodeficient mice. The main routes of invasion were long-distance migration along white matter tracts and local migration along blood vessels. We found that GBM cells of most tumors (6/8) do not associate with blood vessels, as observed for migrating NPCs. These tumors, derived from low lamin A/C expressing GBM cells, were comparatively highly diffusive and invasive. On the other hand, 2/8 tumors showed perivascular invasion and displacement of astrocyte end-feet, migrated less diffusively, grew as a solid tumor, and were characterized by high expression of lamin A/C. We conclude that the migration pattern of glioblastoma is tumor cell-specific, and that the ability to invade the narrow spaces within white matter tracts may require low expression of lamin A/C leading to increased nuclear plasticity. This study highlights the role of GBM heterogeneity in driving the aggressive growth of glioblastoma.