Comparing angiogenic and invasive glioblastoma gene networks. Thrombospondin-1 as the highest connected invasive gene.

Glioblastoma (GBM) is a highly heterogeneous angiogenic tumour that exhibits a pronounced invasive behaviour. We undertook a systematic study and focused on the matricellular protein Thrombospondin-1 (THBS1) to uncover molecular mechanisms underlying the role of THBS1 in GBM development. In patient samples, THBS1, was found increased with glioma grade which correlated with high TGF-b activity. RNA sequencing of patient-derived xenograft tissue from laser capture micro-dissected peripheral and central tumour areas demonstrated that THBS1 was one of the gene with the highest connectivity at the tumour borders. All in all, these data show that TGF-b induces THBS1 expression via Smad3 which contributes to the invasive behaviour and GBM expansion.