Urokinase Expression and Binding Activity Associated With the Transforming Growth Factor b1-Induced Migratory and Invasive Phenotype of Mouse Epidermal Keratinocytes
Santibañez, Juan Francisco
Cita de ítem
Journal of Cellular Biochemistry 74:61–73 (1999)
Transforming growth factor b1(TGF-b1) is a stimulator of malignant progression in mouse skin carcinogenesis.
TGF-b1 exerts a differential effect on cultured nontumorigenic (MCA3D cell line) and transformed (PDV cell
line) keratinocytes. Whereas MCA3D cells are growth arrested and committed to die in the presence of the factor, it
induces a reversible epithelial-fibroblastic conversion in PDV cells. This conversion is associated in vivo with a
squamous-spindle cell carcinoma transition. Here we have investigated the role of urokinase (uPA) during malignant
progression of transformed epidermal keratinocytes. We show that the levels of uPA expression/secretion, and the uPA
binding activity to the cell surface, correlate with the invasive and malignant potentials of mouse epidermal cell lines.
TGF-b1 enhanced uPA production, the number of uPA cell surface binding sites, and the expression of the plasminogen
activator inhibitor PAI-1, in transformed PDV cells, but had no major effect on nontumorigenic MCA3D keratinocytes.
Increased uPA production depended on the presence of the factor in the culture medium and occurred concomitantly to
the stimulation of the migratory and invasive abilities of PDV cells. Synthetic peptides containing the amino terminal
sequence of the mature mouse uPA inhibited the binding of uPA to the cell surface and decreased TGF-b1-induced cell
motility and invasiveness. These results demonstrate that the uPA system mediates at least part of the migratory and
invasive phenotype induced by TGF-b1 in transformed keratinocytes, and suggest a role for uPA on the changes that lead
to the appearance of spindle carcinomas.