title: A deficiency of uPAR alters endothelial angiogenic function and cell morphology.
abstract: The angiogenic potential of a cell requires dynamic reorganization of the cytoskeletal architecture that involves the interaction of urokinase-type plasminogen activator receptor (uPAR) with the extracellular matrix. This study focuses on the effect of uPAR deficiency (uPAR-/-) on angiogenic function and associated cytoskeletal organization. Utilizing murine endothelial cells, it was observed that adhesion, migration, proliferation, and capillary tube formation were altered in uPAR-/- cells compared to wild-type (WT) cells. On a vitronectin (Vn) matrix, uPAR-/- cells acquired a "fried egg" morphology characterized by circular actin organization and lack of lamellipodia formation. The up-regulation of β1 integrin, FAK(P-Tyr925), and paxillin (P-Tyr118), and decreased Rac1 activation, suggested increased focal adhesions, but delayed focal adhesion turnover in uPAR-/- cells. This accounted for the enhanced adhesion, but attenuated migration, on Vn. VEGF-enriched Matrigel implants from uPAR-/- mice demonstrated a lack of mature vessel formation compared to WT mice. Collectively, these results indicate that a uPAR deficiency leads to decreased angiogenic functions of endothelial cells.
authors.affiliation: W, M, Keck Center for Transgene Research, University of Notre Dame, 230 Raclin-Carmichael Hall, Notre Dame, Indiana 46556, USA. vploplis@nd.edu.
authors.forename: Rashna D
authors.initials: RD
authors.lastname: Balsara
authors.forename: Reid
authors.initials: R
authors.lastname: Merryman
authors.forename: Farhaad
authors.initials: F
authors.lastname: Virjee
authors.forename: Claire
authors.initials: C
authors.lastname: Northway
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Ploplis