Extravascular migration of tumor cells in the brain: an electron microscopic study

The mechanisms of extravasation of rat ascites hepatoma AH7974 cells arrested in the cerebral capillaries of Donryu strain rats were studied by transmission electron microscopy. Until 2 days after the injection of tumor cells into the carotid artery, the surfaces of tumor cells were generally smooth without microvilli. At 3 and 4 days after injection, some of the tumor cells formed filopodia in regions facing the endothelial cells. These protrusions were in front as the cells left the vessel. First, the tumor cells inserted these cytoplasmic projections into the endothelial cell lining until they completely breached endothelial cells, or caused fragmentation of the endothelium resulting in the exposure of underlying basal lamina. Next, the tumor cells appeared to push the endothelial cells aside and attach directly to the basal lamina. They penetrated the basal lamina by producing small (0.07-1.8 micron) pores through which they thrusted cytoplasmic projections. Finally, the tumor cells migrated by cytoplasmic streaming through the pores in the basal lamina to complete the extravascular process.