In vitro anti-proliferative and anti-invasive role of aminoterminal fragment of urokinase-type plasminogen activator on 8701-BC breast cancer cells.
8701-BC cells, derived from a primary carcinoma of the breast, constitutively express mRNA for urokinase-type plasminogen activator (uPA). In this paper, we demonstrated the presence of uPA in the conditioned medium, and of uPA-receptor (uPAR) on the cell surface of 8701-BC cells, which therefore have the potential for an autocrine mechanism of uPA-mediated stimulation. We examined whether exogenous addition of either intact uPA, or its amino-terminal fragment (uPA-ATF), which lacks catalytic activity but retains the uPAR binding site and a growth factor-like domain, or immunoneutralisation of endogenous uPA-uPAR interactions could exert any effect on the proliferative and invasive behaviour of 8701-BC cells. The data demonstrate that, while uPA promotes growth and invasion of 8701-BC cells, its effect reversed by blocking uPA-uPAR interactions, uPA-ATF not only fails to impart growth factor-like signals, but also restrains cell invasion in vitro. In the light of these and other data, an active participation of ATF in the complex cell-ECM network of interactions underlying cancer progression can be postulated. In addition, it appears worth considering the possibility of testing the effect of this uPA fragment in vivo for the therapy of breast (and possibly other) human invasive carcinomas.
Luparello
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C
Dipartimento di Biologia Cellulare e dello Sviluppo, Università, Palermo, Italy.
Del Rosso
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M
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry*; D006801:Humans; D009361:Neoplasm Invasiveness; D010446:Peptide Fragments / Q000494:pharmacology; D010960:Plasminogen Activators / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology
D003470:Culture Media; C524898:PLAUR protein, human; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator