Abstract 1493: Tumor-associated soluble uPAR enhances endothelial cell migration by staffing into lipid rafts

Abstract The expression of urokinase plasminogen activator receptor (uPAR), a heavily glycosylated glycosyl-phosphatidylinositol (GPI)-anchored cell surface receptor, induces cell migration, and its expression correlates with the malignant phenotype of various cancers. The soluble form of uPAR (s-uPAR), which is found in the circulation of cancer patients, is associated with tumor malignancy and serves as a prognostic marker for various cancers. As such, in the current study, we analyzed the effect of s-uPAR from glioblastoma tumor cell conditioned medium (TCM) on endothelial cell migration. Here, we present evidence that s-uPAR from tumor cells augments migration and invasion on vitronectin and fibronectin matrices of human umbilical vein endothelial cells (HUVEC). The membrane fraction of HUVEC, which were cultured on TCM, had increased amounts of s-uPAR recruited into the membranes of endothelial cells. Co-localization studies for GM1 ganglioside receptor (a lipid raft marker) and uPAR further demonstrated s-uPAR recruitment into lipid rafts of HUVEC. Further, western blot analysis for uPAR in lipid raft fractions from HUVEC cells grown on TCM confirmed s-uPAR recruiting onto HUVEC cell membranes. Moreover, the addition of functional blocking uPAR antibodies to TCM mitigated s-uPAR-enhanced HUVEC migration and invasion. Our data suggest that s-uPAR from tumor cells might be involved in the recruitment of endothelial cells in the tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1493. doi:10.1158/1538-7445.AM2011-1493