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 orthotopic (kidney) and ectopic (subcutaneous) organs. The KG-2 cells implanted in the kidney produced local tumors and lung metastases, whereas those implanted subcutaneously produced only local tumors. The production of u-PA was determined by immunohistochemistry and an enzyme-linked immunosorbent assay (ELISA). High levels of u-PA were produced by the metastatic kidney tumors and lung metastases, whereas the subcutaneous tumors produced low levels. KG-2 cells co-cultured with mouse kidney or lung fibroblasts produced higher levels of u-PA than KG-2 cells co-cultured with mouse skin fibroblasts. Furthermore, KG-2 cells cultured with the conditioned medium from mouse kidney or lung fibroblasts produced higher levels of u-PA than KG-2 cells cultured with the conditioned medium from mouse skin fibroblasts. The results indicate that the expression of u-PA by KG-2 cells is one of the important factors that determine their metastatic potential and that the production of u-PA is influenced by the organ microenvironment, including soluble factors produced by surrounding fibroblasts.
Gohji
K
K
Department of Urology, Kobe University School of Medicine, Japan.
Nakajima
M
M
Boyd
D
D
Dinney
C P
CP
Bucana
C D
CD
Kitazana
S
S
Kamidono
S
S
Fidler
I J
IJ
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000556:secondary*; D018920:Coculture Techniques; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology* / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis*
D014568:Urokinase-Type Plasminogen Activator