Expression Of Urokinase-Type Plasminogen Activator (uPA), Its Receptor (uPAR) And Its Inhibitor (PAI-1) In Russian And American Patients With Colon Carcinoma. James L. Wittliff¹, Andrei S. Smolenkov², Coskun Tecimer¹, Gerald A. Schmitt¹, Wayne B. Tuckson³ and Susan Galandiuk³.

¹Brown Cancer Center & ³Dept. of Surgery, University of Louisville, Louisville, KY and ²Perm Regional Clinical Hospital, Perm Russia.

Tissue remodeling during trophoblast invasion and breast involution involves several proteases which have emerged as markers of breast cancer invasion and metastasis. uPA converts plasminogen to plasmin and functions as an ectoenzyme. PAI-1, a member of the serpin superfamily, reacts rapidly with uPA even when it is associated with its receptor, uPAR, on the surface of target cells. In preparation for evaluation of these putative prognostic markers in studies between our institutions, the levels and distribution of the three analytes were measured with an ELISA method (American Diagnostica, Inc.). Extracts were prepared in 1% Triton X-100 in 20 mM Tris-HCl buffer, pH 8.5 containing 125 mM NaCl. Stability of analytes in extracts frozen at -86C was determined to be >60 days. Contamination of tissue biopsies by blood cells and plasma known to contain proteases did not alter analyte levels in control experiments when extracts were maintained on ice and analyzed within 2 hr of thawing. Results from colon biopsies of 15 male and 16 female American patients were compared with those of 21 male and 15 female Russian patients. Neither patient's sex, age nor site of residence appeared to influence the level of expression of either uPA or uPAR. However, when PAI-1 was evaluated in a comparison of results using a statistic with equal and unequal variance, there appeared to be a difference in levels between 1) American & Russian men and 2) American & Russian women. The patient population will be increased to evaluate these preliminary findings so that a clinical study may be conducted between our institutions to evaluate the prognostic significance of uPA, uPAR and PAI-1 in colon carcinoma.

Research supported in part by a grant from American Diagnostica, Inc.