Expression and regulation of neuropilin-1 in human astrocytomas

Vascular endothelial growth factor (VEGF), through activation of its endothelial receptors VEGFR-1 and VEGFR-2, is an important positive modulator of tumor angiogenesis and edema in solid tumors such as malignant astrocytomas. Neuropilin-1 (Npn-1) is a transmembrane receptor expressed by both endothelial and non-endothelial cells, including tumor cells. Npn-1 has been postulated to function as a co-factor in activation of the biologically relevant VEGFR-2, by the most abundant VEGF165 isoform. However, the function of Npn-1 in normal and pathological angiogenesis, its expression pattern in relation to VEGF in tumors such as astrocytomas and whether it is similarly or differentially regulated compared to VEGF remain unknown. In our study, the expression pattern of Npn-1 and VEGF by human astrocytoma cell lines and specimens was closely correlated and associated with malignant astrocytomas. Mitogens, such as epidermal growth factor and activation of p21-Ras, previously demonstrated to be relevant in astrocytoma proliferation and induction of VEGF, also induce Npn-1 expression. Hypoxia, the main physiological inducer of VEGF expression, decreased Npn-1 expression. Increased Npn-1 expression was also demonstrated in a transgenic mouse astrocytoma model. Astrocytomas are an ideal system for furthering our understanding of the functional relevance, if any, of Npn-1 in tumor angiogenesis.