Rheumatoid synovial fibroblasts constitutively express the fibrinolytic pattern of invasive tumor-like cells.
OBJECTIVE
In rheumatoid arthritis (RA) the synovial membrane proliferates and invades the underlying tissues. The cell-associated fibrinolytic system (urokinase-type plasminogen activator, uPA; uPA receptor, uPAR; plasminogen activator inhibitor-type 1, PAI-1) is pivotal in cell invasion and proliferation. For this reason, the expression and the role of such enzymatic system was investigated in synovial fibroblasts (SF) of normal and RA patients.


METHODS
In SF obtained from RA patients and control subjects, uPA, uPAR and PAI-1 were measured by ELISA of cell lysates and culture medium and by RT-PCR of mRNAs. uPA was also studied by zymography. Proliferation was measured by cell counting and cell invasion with the Boyden chamber.


RESULTS
RA-SF over-express uPAR and PAI-1 and are more prone than the normal counterpart to spontaneous and uPA-challenged invasion and proliferation, which are counteracted by antagonists of the fibrinolytic system.


CONCLUSIONS
RA-SF display the fibrinolytic pattern and behaviour of invasive tumor-like cells. Antagonists of the fibrinolytic system are able to revert growth and invasion of both normal and RA-SF.
Guiducci
S
S
Department of Medicine, Division of Rheumatology University of Florence, Florence, Italy.
Del Rosso
A
A
Cinelli
M
M
Margheri
F
F
D'Alessio
S
S
Fibbi
G
G
Matucci Cerinic
M
M
Del Rosso
M
M
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002633:Chemotaxis; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator