by ecancer reporter Clare Sansom

Glioblastomas are the most common, and also the most aggressive, of adult brain tumours. They are derived from glial cells, non-neuronal cells that provide protection for neurons in the brain. They are also some of the most highly angiogenic of tumours. In normal brain tissue, neural stem cells are known to be able to differentiate into vascular endothelial cells. A group of Italian researchers has now shown that endothelial cells in the tumour vasculature can arise from the same population of stem-like cells that gives rise to the cells that form the glioblastoma. This has led them to propose a new mechanism for angiogenesis that may be found in other solid tumour types.

The researchers selected from tissue archives a group of glioblastomas characterised by high levels of angiogenesis and accumulation of mutant p53 in tumour cell nuclei. Endothelial cells in these tumours were probed for tumour-like chromosomal aberrations using immunofluorescence and fluorescence in situ hybridization (FISH). Probes for aberrations common in glioblastomas revealed that a fraction of endothelial cells in all tumours with one of these large mutations carried the same mutation as the associated tumour tissue. Over all the samples between 20% and 90% of endothelial cells showed tumour-specific changes in their chromosomes. This suggested that these endothelial cells may have the same origin as the glioblastoma cells.

In general terms, the concept of the “cancer stem cell” is still fairly ill defined. Glio-blastomas, however, are now known to be maintained by a population of glioblastoma stem-like cells (GSCs) that can differentiate into a number of tumour-associated cell types. To determine whether the vascular endothelial cells with tumour-like chromosomal characteristics were also derived from GSCs, the researchers cultivated glioblastoma neurospheres enriched in GSCs and normal glioblastoma cells in conditions known to promote angiogenesis. The neurospheres, but not the cultured glioblastoma cells, generated progeny with characteristics of endothelial cells. Furthermore, when the same glioblastoma neurospheres were injected into immunodeficient NOD/SCID mice they grew into highly vascularised tumours. The cells comprising the vasculature of these tumours were found to be of human origin, and so to have derived from the neurospheres; this essentially replicates the in vitro results in vivo.

Together, these results show that NSCs, like normal neural stem cells, are able to differentiate into endothelial cells and that this contributes to the growth of the tumour vasculature, which is well developed in glioblastoma. This would represent a new mechanism for tumour angiogenesis that may not be restricted to glial tumours. Endothelial cells bearing tumour-like mutations have already been observed in other cancers including neuroblastoma and lymphoma, although the origin of these cells has not yet been determined.

Reference

Vitiani, L., Pallini, R., Biffoni, M. and 8 others (2010). Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature epub ahead of print 25 November 2010, doi:10.1038/nature09557.