Secretion of plasminogen activators by XXXX colorectal and @entity356 explants.

@entity1 @entity5 @entity2 @entity1351 @entity14 @entity3 @entity880 @entity694 @entity356
Conditioned media from explants of @entity1 @entity14 in short-term organ culture were analysed for plasminogen activator activity, activity toward the synthetic urokinase substrate, Spectrozyme-UK, and for the presence of urokinase antigen using monospecific goat antibody, by enzyme-linked immunosorbent assay. Comparisons were made between @entity5 , adjacent normal mucosa and metastatic lesions. These analyses were carried out on unfractionated culture fluids and on fractions obtained by fast protein liquid chromatography separation using Superose 6 gels. Plasminogen activator activity, tested by azocaseinolysis in the presence of added plasminogen, was restricted to peaks of 55 kD and 155 kD. These were of the urokinase type as shown by specific immunoinhibition and by absorption by an antiurokinase antibody-Affigel 10 column. Spectrozyme-UK, in addition to these peaks, detected a series of higher molecular weight activities, the largest of which appeared in the void volume, and were therefore of greater than 10(6) molecular weight. These activities were greatly increased by inclusion of trace @entity1351 indicating that these components were mostly in their proenzyme forms. The characteristics of these very large enzymes were similar to those isolated earlier from a @entity1 @entity2 cell line. Comparison of the primary and @entity3 confirmed earlier observations showing that urokinase secretion by the @entity3 was greatly reduced in comparison with the @entity5 : in the @entity694 it was 10 per cent of the value for the primary, in the @entity356 3 per cent, whether means or medians were compared (P less than 0.0001). This large difference was characteristic only of plasminogen activator secretion assayable by azocaseinolysis; activities toward Spectrozyme-UK, and antigen reacting with anti-urokinase antibody, were considerably less different in the two groups. In individual tissues, no correlation was found between the amount of extractable plasminogen activator and amounts secreted, or between the latter and the amount of @entity880 released. It is postulated that the greatly reduced plasminogen activator secretion by explants of @entity3 may be a phenotypic characteristic of distinct advantage for @entity5 cells destined to initiate metastatic foci, and may contribute to the ability of circulating @entity5 cells to lodge in the blood vessels of the target organ.
