gms | German Medical Science

Objective: Medulloblastoma (MB) is the most common childhood malignant brain tumour. Neoangiogenesis seams to be a critical factor for tumour growth and progression and a pre-requisite for metastases. VEGF is one of the most powerful mitogen for endothelial cells in central nervous system tumours. The different isoforms bind to two tyrosine kinase receptors (Flt-1 or VEGFR-1 and KDR or VEGFR-2) and, upon binding, the receptor is phosphorylated thus triggering the intracellular transduction signal pathway. Although VEGF receptors were initially found on endothelial cells, recent studies have shown that tumour cells of different origins express VEGF receptors too. This suggests that VEGF may act as an autocrine signal. We investigated the role of VEGF/VEGFR signaling on MB cell growth.

Methods: 13 paraffin embedded cases of classic MB were analyzed to determine expression of VEGF, VEGFR-1 and VEGFR-2. Transcript and protein expression of the same targets were also analyzed by RT-PCR and western-blot techniques on 3 MB cell lines, along with their functional status.

Results: Cells of our MB cases showed an intense and diffuse cytoplasmic expression of VEGF. VEGFR-1 expression was lower and more heterogeneous than VEGF but with several cells reacting intensively. VEGFR-2 expression was lower than VEGF and VEGFR-1. All targets showed a stronger staining in the interfollicular than in the follicular areas. Positive reaction for VEGF and its receptors was also seen around the endothelia of tumour-supplying vessels. Semiquantitative analysis of VEGF and VEGFR expression was also performed and generally showed moderate to high expression levels. VEGF and its receptors were expressed in all the MB cell lines and were functional.

Conclusions: Immunohistochemical analysis of MB specimens and the in vitro studies of MB cell lines support an autocrine role of VEGF in vivo given the concomitant expression of VEGF and its cognate receptors in MB cells.