Expression and regulation of neuropilin-1 in human astrocytomas

Vascular endothelial growth factor (VEGF), through activation of its endoth elial 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-l) is a transmembrane receptor expressed by both endoth elial and non-endothelial cells, including tumor cells. Npn-l has been post ulated to function as a co-factor in activation of the biologically relevan t VEGFR-2, by the most abundant VEGF165 isoform. However, the function of N pn-1 in normal and pathological angiogenesis, its expression pattern in rel ation to VEGF in tumors such as astrocytomas and whether it is similarly or differentially regulated compared to VEGF remain unknown. In our study, th e expression pattern of Npn-l 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, prev iously demonstrated to be relevant in astrocytoma proliferation and inducti on of VEGF, also induce Npn-l expression. Hypoxia, the main physiological i nducer of VEGF expression, decreased Npn-l expression. Increased Npn-l expr ession was also demonstrated in a transgenic mouse astrocytoma model. Astro cytomas are an ideal system for furthering our understanding of the functio nal relevance, if any, of Npn-l in tumor angiogenesis, (C) 2000 Wiley-Liss, Inc.