Reversible cellular adhesion to vitronectin linked to urokinase receptor occupancy

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• Urokinase receptors (uPAR) focus pericellular proteolysis, crucial for cell migration and tissue remodeling.
• uPAR engagement also enhances leukemic cell adhesion, particularly when cells are stimulated by cytokines.
• The specific molecular components mediating this uPAR-dependent adhesion remain incompletely understood.

Purpose of the Study:

• To investigate the role of serum or matrix components in urokinase receptor-mediated cell adhesion.
• To characterize the interaction between cytokine-stimulated human myelomonocytic cells and vitronectin via the urokinase receptor.

Main Methods:

• Stimulation of human myelomonocytic cells with cytokines.
• Assessing cell adhesion to immobilized and soluble vitronectin.
• Characterizing the binding kinetics and dependencies (cation, RGD) of the vitronectin receptor.
• Investigating the coupling of urokinase receptor occupancy to adhesion and proteolysis.

Main Results:

• Cytokine-stimulated cells express a high-affinity receptor for urea-purified vitronectin (Kd < 10 nM).
• This receptor binding is independent of divalent cations and the Arg-Gly-Asp (RGD) sequence.
• Adhesion occurs with plastic-adsorbed vitronectin (both urea-purified and native), but not with soluble native vitronectin.
• Receptor activity is tightly linked to urokinase receptor occupancy, inducing selective and reversible adhesion to matrix vitronectin.

Conclusions:

• Urokinase receptor binding induces specific cellular adhesion to the matrix form of vitronectin.
• This process is independent of typical adhesion motifs, suggesting a unique interaction mechanism.
• The findings reveal a novel binding cycle where uPAR occupancy coordinates cell adhesion and pericellular proteolysis, impacting cell migration and tissue remodeling.