The human guanylate binding protein-1 (hGBP-1) characterizes inflammatory cytokine (IC)-activated blood vessel endothelial cells (EC) and regulates the antiangiogenic activity of IC in these cells in vitro and in vivo. In addition, hGBP-1 is the first GTPase which has been observed to be secreted. In colorectal carcinoma, the expression of hGBP-1 in the tumour stroma has been shown in a recent work to be an independent prognostic factor associated with a better outcome. The project focuses on the specific role of hGBP-1 in this context. The objectives of the are: (1) to characterize the mechanisms of hGBP-1 secretion, (2) to study the biological effects of the secreted protein and (3) to investigate the potential in vivo function of secreted hGBP-1. The methodological approach would consist first in the determination of the protein domains responsible of the secretion, to define the non classical secretion pathway involved and to test the association of hGBP-1 with endothelial cells microparticles. Then, the biological effects of extracellular hGBP-1 will be investigated, as well as the existence of a receptor. Finally, the tumours collected in two previous xenotransplant mouse experiments with induced expression and secretion of hGBP-1 will be analyzed for hGBP-1 expression, proliferation and angiogenesis. The long term goal of the project is to exploit the results obtained for new therapeutic applications for the treatment of cancer or infectious diseases.