Abstract
The question whether perivascular glioma cells invading the brain far from the tumor bulk may disrupt the blood–brain barrier (BBB) represents a crucial issue because under this condition tumor cells would be no more protected from the reach of chemotherapeutic drugs. A recent in vivo study that used human xenolines, demonstrated that single glioma cells migrating away from the tumor bulk are sufficient to breach the BBB. Here, we used brain xenografts of patient-derived glioma stem-like cells (GSCs) to show by immunostaining that in spite of massive perivascular invasion, BBB integrity was preserved in the majority of vessels located outside the tumor bulk. Interestingly, the tumor cells that invaded the brain for the longest distances traveled along vessels with retained BBB integrity. In surgical specimens of malignant glioma, the area of brain invasion showed several vessels with preserved BBB that were surrounded by tumor cells. On transmission electron microscopy, the cell inter-junctions and basal lamina of the brain endothelium were preserved even in conditions in which the tumor cells lay adjacently to blood vessels. In conclusion, BBB integrity associates with extensive perivascular invasion of glioma cells.
Highlights
Malignant gliomas are highly invasive cancers.The sub-cortical white matter and inter-hemispheric tracts, like the corona radiata and corpus callosum, are major paths for tumor spreading
A recent study that used clinically relevant xenograft models demonstrated that human glioma cells are able to migrate far away from the main tumor mass travelling between the endothelial cells and the endfeet of astrocytes, where even single glioma cells are sufficient to cause a focal breach of the blood–brain barrier (BBB) [5]
The GSC1 cell line had been established from a GBM of the proneural subtype and was molecularly characterized as a Glioma Stem full (GSf), a genotype that closely resemble the proneural one [9]
Summary
A recent study that used clinically relevant xenograft models demonstrated that human glioma cells are able to migrate far away from the main tumor mass travelling between the endothelial cells and the endfeet of astrocytes, where even single glioma cells are sufficient to cause a focal breach of the blood–brain barrier (BBB) [5]. These results may carry important clinical implications and may refuel aggressive chemotherapy for treating brain areas of tumor infiltration. We questioned whether the invading perivascular glioma cells do disrupt the BBB away from the tumor bulk, a condition whereby these cells would be no more protected from the reach of chemotherapeutic drugs
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