Abstract 1292: Broad vascular distribution of Neuropilin-1 and its ligands in human tumors

Neuropilin-1 (NRP1) is a multi-domain transmembrane receptor that is important for the development of the nervous and vascular systems and has been implicated in modulating various aspects of tumor biology. We have previously shown that an antibody directed against NRP1 inhibits tumor growth and reduces tumor angiogenesis, as a single agent and more potently in combination with anti-VEGF. Currently, anti-NRP1 is in evaluation in early clinical studies. Therefore, understanding the expression pattern of Nrp1 and its relevant ligands in human tumor samples is of critical importance. To this end, we first evaluated the binding of a number of putative ligands that have been suggested to interact with NRP1 in the literature, and furthermore to understand which of these are biochemically or functionally inhibited by our anti-NRP1. We found that members of the semaphorin and VEGF families, but not HGF bind to NRP1. However, only binding and function of specific ligands from the VEGF family are inhibited by anti-NRP1. Additionally, we evaluated the expression pattern of NRP1 in human tumor samples from a number of different tumor types, including breast, colorectal, lung, ovarian, pancreatic, prostate and renal cancer. NRP1 is broadly expressed in the vasculature of most cases of all these tumor types. Additionally, NRP1 is also variably expressed by tumor cells and other stromal elements in a more variable manner that is tumor type dependent. These results suggest that NRP1 is a potentially important therapeutic target in many different tumor types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1292.