Grant: Operating Grant - Priority Announcement: Infection and Immunity (Bridge Funding)

Neuropilin-1 (Nrp1) is a multifunctional protein that plays an important role in many processes such as the formation of new blood vessels (angiogenesis) and the development of the nervous system. However, new studies reveal that it is capable of many other activities. Recently, we found that Nrp1 is a receptor for transforming growth factor-beta (TGF-beta). TGF-beta is a cytokine (soluble mediator that regulates immune functions) that plays a key role in immunity, angiogenesis and wound healing. However, it can also exert negative effects in several diseases resulting, for example, in organ failure (lungs, kidneys, heart), and the promotion of cancer progression and metastasis. We have shown that the interactions between Nrp1 and TGF-beta contribute to the proper regulation of the immune system, and identified some molecular mechanisms that may explain these effects. Furthermore, we found that breast cancer cells, which express Nrp1, capture TGF-beta and respond to this cytokine, and we believe that this increases their malignant potential. Therefore, we propose experiments to further study the mechanisms of action of Nrp1, and its role in immune regulation and cancer. Significance. Nrp1 is a multifunctional protein that interacts with several growth factors and/or their receptors. We propose to study novel interactions with TGF-beta that we hypothesize play important roles in immune regulation and tumour biology. These studies could lead to new therapies for cancer.