Analyzes of the role of urokinase receptor cell growth

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(1) We studied the expression of uPAR mPNA in cultured cell line (U-937). The expression of uPAR mRNA was enhanced by phorbol-ester stimulation, which resulted in the higher accumulation of uPAR antigen both in the medium and in the cell lysate. We detected two different forms of uPAR mRNA,one of which coodes mature uPAR and another codes soluble uPAR.Employing two different DNA probes, each of which detects only one of these two different mRNAs, we demonstrated that both forms increased after phorbol ester stimulation.(2) We assayd antigen levels of soluble uPAR in cancer patients plasma. In lung cancer patients, plasma soluble uPAR levels were significantly higher than those in normal controls. Either by proteolytic cleavage of mature uPAR or by increasing alternatively spliced mRNA for soluble uPAR,plasma uPAR seems to be elevated. Plasma soluble uPAR level might be a useful tumor marker of lung cancer.(3) The expression of uPA mRNA in lung cancer tissue was significantly higher than that in normal lung tissue. The expression of uPAR mRNA,however, did not differ between cancer tissue and normal lung tissue. mRNA of both PAI-1 and PAI-2 were also higher in lung cancer tissue than those in normal counter parts, which are in accordance with our previous results of their antigen level.(4) We analyzed the effects of either uPA alone or of uPA together with its specific inhibitor on cell growth using U937. uPA alone slightly enhanced cell growth. Simultancous use of its inhibitor, however, did not influence cell growth. Since U937 without treatment by phorbol-ester may not have enough amounts of uPAR on cell surface, further experiment using other cell line must be needed to clarify the effect of uPA and its inhibitors on cell growth.