INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

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

Show full item record

Bookmark or cite this item: http://hdl.handle.net/10027/11169

Files in this item

File Description Format
PDF oncsis201319a.pdf (5MB) Main Article PDF
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, http://www.nature.com/oncsis/index.html. 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 http://creativecommons.org/licenses/by-nc-nd/3.0/
URI: http://hdl.handle.net/10027/11169
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
 

This item appears in the following Collection(s)

Show full item record

Statistics

Country Code Views
United States of America 406
China 109
Russian Federation 42
Germany 25
Ukraine 16

Browse

My Account

Information

Access Key