Premium
Urokinase expression and binding activity associated with the transforming growth factor β 1 ‐induced migratory and invasive phenotype of mouse epidermal keratinocytes
Author(s) -
Santibáñez Juan F.,
Frontelo Pilar,
Iglesias Maite,
Martínez Jorge,
Quintanilla Miguel
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990701)74:1<61::aid-jcb7>3.0.co;2-b
Subject(s) - phenotype , transforming growth factor , microbiology and biotechnology , urokinase , epidermal growth factor , expression (computer science) , biology , cancer research , growth factor , cell culture , genetics , receptor , gene , computer science , programming language
Transforming growth factor β 1 (TGF‐β 1 ) is a stimulator of malignant progression in mouse skin carcinogenesis. TGF‐β 1 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‐β 1 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‐β 1 ‐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‐β 1 in transformed keratinocytes, and suggest a role for uPA on the changes that lead to the appearance of spindle carcinomas. J. Cell. Biochem. 74:61–73, 1999. © 1999 Wiley‐Liss, Inc.