ORGAN-SITE DEPENDENCE FOR THE PRODUCTION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR AND METASTASIS BY HUMAN RENAL-CELL CARCINOMA-CELLS

We examined the role of urokinase-type plasminogen activator (u-PA) in the metastasis of the human renal cell carcinoma (HRCC) implanted in athymic nude mice. Cells from a HRCC KG-2 line were implanted in ortho topic (kidney) and ectopic (subcutaneous) organs. The KG-2 cells impla nted in the kidney produced local tumors and lung metastases, whereas those implanted subcutaneously produced only local tumors. The product ion of u-PA was determined by immunohistochemistry and an enzyme-linke d immunosorbent assay (ELISA). High levels of u-PA were produced by th e metastatic kidney tumors and lung metastases, whereas the subcutaneo us tumors produced low levels. KG-2 cells co-cultured with mouse kidne y or lung fibroblasts produced higher levels of u-PA than KG-2 cells c o-cultured with mouse skin fibroblasts. Furthermore, KG-2 cells cultur ed with the conditioned medium from mouse kidney or lung fibroblasts p roduced higher levels of u-PA than KG-2 cells cultured with the condit ioned medium from mouse skin fibroblasts. The results indicate that th e expression of u-PA by KG-2 cells is one of the important factors tha t determine their metastatic potential and that the production of u-PA is influenced by the organ microenvironment, including soluble factor s produced by surrounding fibroblasts.