MODULATION OF MURINE-B16F10 MELANOMA PLASMINOGEN-ACTIVATOR PRODUCTIONBY A SYNTHETIC PEPTIDE DERIVED FROM THE LAMININ-A CHAIN

Citation
Ms. Stack et al., MODULATION OF MURINE-B16F10 MELANOMA PLASMINOGEN-ACTIVATOR PRODUCTIONBY A SYNTHETIC PEPTIDE DERIVED FROM THE LAMININ-A CHAIN, Cancer research, 53(9), 1993, pp. 1998-2004
Citations number
32
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
ISSN journal
0008-5472
Volume
53
Issue
9
Year of publication
1993
Pages
1998 - 2004
Database
ISI
SICI code
0008-5472(1993)53:9<1998:MOMMPP>2.0.ZU;2-K
Abstract
Laminin is a large multidomain protein with diverse biological activit ies. We previously demonstrated that intact laminin as well as an A ch ain synthetic peptide (LamA2091-2108) stimulate tissue plasminogen act ivator (t-PA)-catalyzed plasminogen activation. Here we report that La mA2091-2108 increases t-PA production by the highly metastatic murine melanoma cell line B16F10, with no effect on the parental B16F1 line, which has a low metastatic capacity. Incubation of plasminogen with B1 6F10-conditioned medium results in direct activation of the zymogen to plasmin. Furthermore, following incubation of B16F10 cells with plasm inogen, plasmin is eluted from the cell surface. suggesting that these cells contain binding sites for plasminogen/plasmin in close proximit y to t-PA binding sites. Quantitation of t-PA activity using the synth etic substrate Val-Leu-Lys-p-nitroanilide indicates a minimal 10-fold increase in t-PA in the conditioned medium of B16F10 cells grown in th e presence of LamA2091-2108, with no increased t-PA activity observed in B16F1-conditioned medium. Similar results were obtained in immunoca pture experiments which are specific for t-PA antigen. In addition, B1 6F10 melanoma-associated t-PA catalyzes the plasminogen dependent hydr olysis of laminin. Together these data suggest that degradation of bas ement membrane proteins by metastatic melanoma cells may release fragm ents (such as LamA2091-2108) which stimulate both the production and a ctivity of metastasis-associated proteinases such as t-PA, providing a mechanism for augmentation of the metastatic capacity of B16F10 melan oma cells.