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Am J Pathol. 1997 Dec; 151(6): 1655–1661.
PMCID: PMC1858342
PMID: 9403716

Organ-site dependence for the production of urokinase-type plasminogen activator and metastasis by human renal cell carcinoma cells.

K. Gohji, M. Nakajima, D. Boyd, C. P. Dinney, C. D. Bucana, S. Kitazana, S. Kamidono, and I. J. Fidler
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Abstract

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.

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Selected References

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