Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression

Neuropilin-1 (NRP1) is a VEGF(165) and semaphorin receptor expressed by vas cular endothelial cells (EC) and tumor cells. The function of NRP1 in tumor cells is unknown, NRP1 was overexpressed in Dunning rat prostate carcinoma AT2.1 cells using a tetracycline-inducible promoter. Concomitant with incr eased NRP1 expression in response to a tetracycline homologue, doxycycline (Dox), basal cell. motility, and VEGF(165) binding were increased three- to fourfold in vitro, However, induction of NRP1 did not affect tumor cell pr oliferation. When rats injected with AT2.1/NRP1 tumor cells were fed Dox, N RP1 synthesis was induced in vivo and AT2.1 cell tumor size was increased 2 .5- to 7-fold in a 3-4 wk period compared to controls. The larger tumors wi th induced NRP1 expression were characterized by markedly increased microve ssel density, increased proliferating EC, dilated blood vessels, and notabl y less tumor cell apoptosis compared to noninduced controls. It was conclud ed that NRP1 expression results in enlarged tumors associated with substant ially enhanced tumor angiogenesis.