Rheumatoid synovial fibroblast constitutively express the fibrinolytic pattern of invasive tumor-like cells

Serena Guiducci, Angela Del Rosso, Marina Cinelli, Francesca Margheri, Silvia D'Alessio, Gabriella Fibbi, Marco Matucci Cerinic, Mario Del Rosso

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)364-372
Number of pages9
JournalClinical and Experimental Rheumatology
Volume23
Issue number3
Publication statusPublished - May 2005

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Keywords

  • Fibrinolytic system
  • Invasion
  • PAI-1
  • Proliferation
  • Rheumatoid arthritis
  • Synovial fibroblasts
  • uPA
  • uPAR

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

Guiducci, S., Del Rosso, A., Cinelli, M., Margheri, F., D'Alessio, S., Fibbi, G., Cerinic, M. M., & Del Rosso, M. (2005). Rheumatoid synovial fibroblast constitutively express the fibrinolytic pattern of invasive tumor-like cells. Clinical and Experimental Rheumatology, 23(3), 364-372.