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Tumor-associated soluble uPAR-directed endothelial cell motility and tumor angiogenesis

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Title: Tumor-associated soluble uPAR-directed endothelial cell motility and tumor angiogenesis
Author(s): Rao, J.S.; Gujrati, M.; Chetty, C.
Subject(s): soluble uPAR migration angiogenesis
Abstract: The expression of urokinase-type plasminogen activator (uPA) receptor (uPAR) correlates with the malignant phenotype of various cancers. The soluble form of uPAR (s-uPAR) is present in the circulation of cancer patients, but the role of s-uPAR in endothelial cell migration is poorly understood. Therefore, we examined the role of tumor-associated s-uPAR on endothelial cell motility and angiogenesis. Here, we present evidence that tumor-associated s-uPAR augments the migration of human umbilical vein endothelial cells (HUVECs). When grown on tumor-conditioned medium, the membrane fraction of HUVECs had increased localization of s-uPAR onto its cell membrane. Colocalization studies for GM1 ganglioside receptor and uPAR further demonstrated s-uPAR recruitment onto lipid rafts of HUVECs. Immunoblot analysis for uPAR in lipid raft fractions confirmed s-uPAR recruiting onto HUVECs' membrane. Further, s-uPAR induced Rac1-mediated cell migration while either function-blocking uPAR antibodies or dominant-negative mutant Rac1 expression in HUVECs-mitigated s-uPAR-enhanced cell migration. In addition, orthotopic implantation of uPAR-overexpressing cells resulted in a significant increase in circulating s-uPAR in blood serum and invasive nature of tumor and tumor vasculature in mice. Collectively, this data provide insight into tumor-associated s-uPAR-directed migration of endothelial cells and its subsequent influence on tumor angiogenesis.
Issue Date: 2013-06
Publisher: Nature Publishing Group
Citation Info: Rao JS, Gujrati M, Chetty C. Tumor-associated soluble uPAR-directed endothelial cell motility and tumor angiogenesis. Oncogenesis. 2013 Jun 24;2:e53. doi: 10.1038/oncsis.2013.19.
Type: Article
Description: This is a copy of an article published in Oncogenesis © 2013 Nature Publishing Group, Oncogenesis is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution- NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit
ISSN: 2157-9024
Sponsor: This research was supported by a grant from the National Institute of Neurological Disorder and Stroke (NS047699 to JSR).
Date Available in INDIGO: 2014-02-19

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