Human primary colon carcinomas xenografted into nude mice. II. Modulation of tumor plasminogen activator activity by the host tissue environment.

The characterization and quantitation of plasminogen activators (PAs) expressed by human colon carcinoma cell lines and primary colon carcinomas inoculated into nude outbred (nu/nu) mice, either as subcutaneous or gut-implanted (GI) xenografts, were discussed. The two colon carcinoma cell lines used in this study, Col 112 (moderately differentiated) and Col 115 (poorly differentiated), differ in their PA expression, the former being a urinary-type PA and the latter being a tissue-type PA producer. Both cell lines demonstrate a positive correlation between tumor invasiveness and measured PA activity; subcutaneous xenografts growing as noninvasive pseudobenign tumor masses were associated with low levels of PA activity, whereas GI xenografts exhibiting invasive growth expressed higher PA activity. Furthermore, coinoculation of Col 115 tumor cells sc and GI in the same host induced high levels of PA activity in subcutaneous xenografts, suggesting a stimulatory effect of the GI xenograft on subcutaneous xenograft PA expression. Also, purified murine plasminogen was demonstrated to represent an efficient substrate for tumor-secreted human PA.