Cell invasion is affected by differential expression of the urokinase plasminogen activated/urokinase plasminogen activator receptor system in musclesatellite cells from normal and dystrophic patients

The aim of this study was to evaluate the differential expression and the f unction in cell movement and proliferation of the urokinase plasminogen act ivator (u-PA) system in muscle satellite cells (MSC) of normal individuals and patients with Duchenne muscular dystrophy (DMD). By immunoenzymatic, zy mographic, and radioligand binding methods and by quantitative polymerase c hain reaction of the specific mRNA we have shown that both normal and DMD M SC produce u-PA and the plasminogen activator inhibitor-1 and express u-PA receptors (Le-PAR). During the proliferation phase of their growth-differen tiation program, MSC from DMD patients show more u-PAR than their normal co unterpart, produce more plasminogen activator inhibitor-1, and release low amounts of u-PA into the culture medium. By Boyden chamber Matrigel invasio n assays we have shown that normal MSC are more prone than DMD cells to spo ntaneous invasion but, when subjected to a chemotactic gradient of u-PA, DM D MSC sense the ligand much better and to a greater extent than normal MSG. u-PA also stimulates proliferation of MSG, but no difference is observable between normal and DMD patients. Antagonization of u-PA/u-PAR interaction with specific anti-u-PA and anti-u-PAR monoclonal antibodies and with antis ense oligonucleotides inhibiting u-PAR expression indicates that u-PA/u-PAR interaction is required in spontaneous and u-PA-induced invasion, as well as in u-PA-induced proliferation.