Human malignant astrocytoma xenografts migrate in rat brain: a model for central nervous system cancer research.

Abstract

Fresh cells from two grade 3 human malignant astrocytomas were prelabeled with Phaseolus vulgaris leucoagglutin (PHAL) and then xenografted into freshly made implantation pockets in rat host cerebral cortex. Animals were sacrificed at 7, 14, 21 days, and 1 month postimplantation (DPI). Paraffin sections were double-labeled for the presence of glial fibrillary acidic protein (GFAP), a specific marker for astrocytes and differentiated astrocytoma cells, and PHAL, utilized as a marker for graft-derived cells. Grafted human astrocytoma cells were found on the glia limitans along the entire circumference of the brain, in the corpus callosum, internal capsule, entopeduncular nucleus, optic tract, and median eminence. In addition, astrocytoma cells were observed in the cingulum, habenula, arcuate, and supraoptic nucleus. Astrocytoma cells entered the spaces of Virchow-Robin, and migrated along parenchymal blood vessels and between the ependymal and subependymal layers of the third and lateral ventricles. The corpus callosum was a major migration route for the astrocytoma cells. The presence of basal lamina or parallel nerve fiber bundles was a common factor for these migration routes. The migration of the human astrocytoma xenografted cells in the rat brain followed the spread of human malignant astrocytomas in the human brain and is a valuable basic science tool in brain cancer research.