No abstract

Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, results from a disruption of the balance between stimulatory and inhibitory factors. Here, we show that anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells. This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors. This downregulation may significantly contribute to glioblastoma development, since we show that an increase in TSP-1 expression is sufficient to strongly suppress glioblastoma cell tumorigenicity in vivo.

Little is known about the relationship between genetic recombination mechanisms and loss of tumour suppressor genes in solid tumours. Here, we demonstrate deletion and truncation of both p53 alleles in a primary human glioblastoma and a derived cell line as the combined result of a t(17;20) reciprocal translocation and a 1.1 Mbp genomic deletion on chromosome 17p, starting in intron 4 of the p53 gene and ending at the telomeric CArepeat marker D17S960. These results (i) suggest that genetic instability can lead to loss of tumour suppressor gene function in solid cancers, (ii) provide mapping of one such recombination event at the nucleotide level, and (iii) establish the orientation of the p53 gene on chromosome 17 as: centromere 5' ± 3'-telomere.