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The role of semaphorins and neuropilins in tumour angiogenesis

Final Activity Report Summary - SEMASNEUROPILINANGIO (The role of semaphorins and neuropilins in tumour angiogenesis)

Very little is known about the newly found receptor family of plexins, neuropilins and their ligands semaphorins in cancer progression and neo-angiogenesis. The evaluation of the inhibitory as well as positive function of different semaphorins, neuropilins and plexins are of great importance, which can lead to further studies to investigate the therapeutic possibilities of these molecules. Here, we show that semaphorin 3A (Sema3A) is a potential anti-cancer agent.

A novel strategy - the tumour-homing ability of pro-angiogenic Tie2-expressing monocytes (TEMs) was exploited as delivery vehicles to transport Sema3A to the tumour site. By transplanting hematopoietic progenitors transduced with a Tie2 promoter/enhancer-driven Sema3A gene, we turned TEMs into Sema3A cell vehicles that efficiently inhibited tumour progression by inhibiting angiogenesis. The TEM cell mediated delivery proved to provide the system with the high efficacy and safety. These results illustrate the therapeutic potential of gene-based Sema3A delivery and treatment of cancer.