Cavallaro U, Wu Z, Di Palo A, Montesano R, Pepper M S, Maier J A, Soria M R
Department of Biological and Technological Research, San Raffaele Scientific Institute, Milano, Italy.
FASEB J. 1998 Aug;12(11):1027-34. doi: 10.1096/fasebj.12.11.1027.
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.
纺锤形细胞系TTB最近从BKV/HIV-1 tat转基因小鼠高度血管化的皮肤损伤中分离出来，并显示具有肝细胞生长因子（HGF）的自分泌环。我们发现成纤维细胞生长因子-2（FGF-2）刺激TTB细胞迁移，并促进uPAR在迁移细胞前缘的极化。FGF刺激的TTB细胞呈现典型的迁移表型，细胞呈三角形，同时肌动蛋白应力纤维和平滑肌特异性肌动蛋白异构体分解。抗尿激酶型纤溶酶原激活剂（uPA）或uPA受体（uPAR）的抗体以及中和抗HGF抗体可阻断FGF-2刺激的迁移。后者还抑制了FGF-2处理的TTB细胞表面uPAR的重新定位。这表明FGF-2和HGF之间存在相互作用，可能通过调节细胞表面uPAR的定位来介导TTB细胞迁移。
