Neuropilin-2 (NRP2) is a cell surface receptor that plays a key role in lymphatic development and in regulating inflammatory responses. In many forms of cancer, high NRP2 expression is associated with worse outcomes. NRP2 can interact with multiple ligands and co-receptors to influence their functional roles.
NRP2 Co-receptors and Ligands
NRP2 can bind to multiple ligands and co-receptors to influence various cellular functions. It interacts with type 3 semaphorins and plexins to impact inflammation and neural development, and with forms of vascular endothelial growth factor (VEGF) and their receptors, especially VEGF-C and VEGFR3, which are centrally involved in lymphangiogenesis.
Recent evidence suggests that NRP2 is expressed at robust levels on different immune cell types, especially upon activation, where it may play important roles in migration, phagocytosis and efferocytosis, and cell-to-cell interactions. NRP2 is expressed in various cells of the immune system such as neutrophils, dendritic cells, macrophages, including alveolar macrophages, T cells, and B cells. In addition, elevated NRP2 expression in tumors is frequently associated with a worsened outcome, and has been described to contribute to resistance to oncolytic drugs via the promotion of autophagic mechanisms. This suggests that NRP2 may be an important regulator of biological responses in a number of different disease settings with potential for therapeutic intervention.
aTyr is currently investigating NRP2 receptor biology, both internally and in collaboration with key academic thought leaders, to identify new product candidates for a variety of disease settings, including cancer, inflammation, and lymphangiogenesis.