The role of neuropilin 2 in physiological and pathological angiogenesis and lymphangiogenesis

Abstract

The generation of new lymphatic vessels through lymphangiogenesis has been implicated in many disease states. This process has some overlap with the better studied angiogenesis pathway, but is under distinct molecular control. Specifically, it has been shown that VEGFR-3 and neuropilin-2 are important mediators of lymphangiogenesis. A greater understanding of this process could lead to new therapies for cancer and lymphedemas. We investigated lymphatic vessel growth in a mouse model with a focus on the effects of neuropilin-2 knockout. First, we induced an immunogenic response via delayed-type hypersensitivity to examine lymphangiogenesis in the physiologic state. Our neuropilin-2 knockout mouse model displayed a decreased ability to resolve inflammation on exposure to an allergen. Next, we subcutaneously injected a highly invasive melanoma to examine lymphangiogenesis in the pathologic state. We noted significantly reduced tumor growth in our neuropilin-2 knockout. In addition, the neuropilin-2 knockout mice displayed reduced vessel area in comparison to their wild-type littermates, suggesting that inhibition of neuropilin-2 may prove a potent antitumor therapeutic strategy. These results highlight neuropilin-2's important role as a mediator of physiological and pathological angiogenesis and lymphangiogenesis.