FGF-2 stimulates migration of Kaposi's sarcoma-like vascular cells by HGF-dependent relocalization of the urokinase receptor.
The spindle-shaped cell line TTB was recently isolated from highly vascularized skin lesions of BKV/HIV-1 tat transgenic mice and shown to possess an autocrine loop for hepatocyte growth factor (HGF). We show that fibroblast growth factor-2 (FGF-2) stimulates TTB cell migration and promotes polarization of uPAR at the leading edge of migrating cells. FGF-stimulated TTB cells presented the typical migratory phenotype, with a triangular cell shape and concomitant breakdown of actin stress fibers and smooth muscle-specific actin isoform. FGF-2-stimulated migration was blocked by antibodies against urokinase-type plasminogen activator (uPA) or uPA receptor (uPAR) and by neutralizing anti-HGF antibodies. The latter also inhibited uPAR relocalization at the cell surface of FGF-2-treated TTB cells. This points to a crosstalk between FGF-2 and HGF that might mediate TTB cell migration by modulating the localization of cell surface uPAR.
Department of Biological and Technological Research, San Raffaele Scientific Institute, Milano, Italy. cavallu@dibit.hsr.it
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U
Cavallaro
Z
Z
Wu
A
A
Di Palo
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R
Montesano
M S
MS
Pepper
J A
JA
Maier
M R
MR
Soria
D002460:Cell Line; D002465:Cell Movement; D003599:Cytoskeleton; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D012514:Sarcoma, Kaposi; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D014568:Urokinase-Type Plasminogen Activator