CHANGES IN VEGF EXPRESSION AND IN THE VASCULATURE DURING THE GROWTH OF EARLY-STAGE ETHYLNITROSOUREA-INDUCED MALIGNANT ASTROCYTOMAS IN RATS

Vascular endothelial growth factor (VEGF), a potent angiogenic and vas cular permeability factor, may be important as a mediator of brain tum our progression. However, it is still not clear whether VEGF plays a c ausative role in the early stage of glioma development. We investigate d the relationship between VEGF protein expression (as assayed by immu nohistochemistry) and different morphological parameters reflecting tu mour progression (tumour diameter, vascular density and vascular diame ter) in tumours at various stages. As a tumour model, ethylnitrosourea (ENU)-induced rat malignant astrocytoma was used. Tumours were classi fied by size and level of vascularity estimated by the von Willebrand factor (vWF) staining. Tumours less than 10 mm in diameter were design ated early stage neoplastic lesions. All 34 early astroglial tumours w ere found to be VEGF positive. Increase in the VEGF immunopositive rat e of tumour cells correlated significantly with increase in vascular d ensity and vascular diameter. We suggest that VEGF induces angiogenesi s and growth of microvessels, promoting growth of the early stage mali gnant astrocytoma.