Urokinase Plasminogen Activation System Modulation in Transformed Cell Lines
Diana Culej Bošnjak1, Tihana Balent1, Petra Korać1
1Department of Biology, Faculty of Science, University of Zagreb, Horvatovac 102, 10000 Zagreb, Croatia.
International Journal of Molecular Sciences
|January 25, 2025
Summary
The urokinase plasminogen activation system (uPA) regulates cell behavior. Manipulating its components, urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI1), altered cell migration and spheroid formation.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- The plasminogen activation system (PAS) regulates extracellular protease plasmin activity.
- PAS components include urokinase plasminogen activator (uPA), its inhibitor PAI1, and receptor uPAR.
- PAS is crucial in tissue remodeling and extracellular matrix degradation, impacting physiological and pathological processes.
Purpose of the Study:
- To investigate the role of uPA, PAI1, and uPAR in cellular processes.
- To analyze the effects of overexpressing these PAS components in glioblastoma and HEK 293 cells.
Main Methods:
- Cloning and overexpression of human uPA, PAI1, and uPAR in A1235 and HEK 293 cell lines.
- Analysis of urokinase activity, protein, and RNA expression via Western blot and RTqPCR.
- Assessment of cell proliferation, migration, invasion, adhesion, and dispersal using cell counting, wound-healing, transwell, and spheroid formation assays.
Main Results:
- Transfection with uPA increased urokinase activity and uPA expression.
- PAI1 transfection decreased urokinase activity, increased PAI1 expression, and reduced cell migration.
- HEK 293 cells expressing PAI formed smaller spheroids.
Conclusions:
- The effects of uPA system molecules are interdependent and influenced by the microenvironment.
- Cell-type-specific signaling plays a role in the observed effects of the uPA system.
