Table 2.

Various models studying the mechanisms used by uPAR/soluble uPAR in the induction of tumor angiogenesis.

Model	Outcome	Mechanism
HUVEC cells incubated with tumor conditioned media	Enhanced EC invasion and migration	Soluble uPAR from the tumor conditioned media colocalized in membrane lipid rafts on EC and induced ERK/Rac-1 mediated cellular migration and tube formation [69]
-Human and murine EC stimulated with VEGF -Human EC treated with uPAR inhibitory peptides (blocking of uPAR/integrin interaction) -Murine EC retrieved from uPAR deficient mice	-VEGF stimulation enhanced in vivo and in vitro EC migration -Inhibition or loss of uPAR resulted in impaired EC migration in vitro and in vivo	Upon VEGF stimulation, uPAR and integrins interact and are endocytosed via a clathrin-coated vesicle followed by their redistribution to the leading edge of the cell to focus the proteolytic activity of plasmin at the invading side of the cell [64]
-HEp3 carcinoma cells transfected with uPAR antisense mRNA -HEp3 cells transfected with uPAR overexpression vector	-Tumor dormancy and G0/G1 arrest; decreased association of uPA/uPAR complexes with α5β1 Integrins in uPAR deficient cells -uPAR-rich cells expressed high levels of ERK -uPA/uPAR complexes associated with integrins and exhibited increased tumor migration and progression	High levels of uPAR lead to increased levels of integrins and enhanced adhesion to fibronectin, thus fibronectin-dependent activation of ERK and stimulation of cellular proliferation [62]
HUVEC cells transfected with uPAR small-interfering RNA; subsequent VEGF treatment	-Compromised VEGFR2 signaling -Inhibition of VEGF-induced angiogenesis -Addition of VEGF to HUVECs induced VEGF signaling and angiogenesis	VEGF prompts the interaction of VEGFR2 with uPAR; uPAR then induces the endocytosis of the complex and the activation of VEGFR2 signaling [66]