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Transforming growth factor-β1 (TGF-β1) has a biphasic effect on the growth of renal epithelial cells. In transformed cells, TGF-β1 appears to accelerate the proliferation of malignant cells. The diverse cellular functions of TGF-β1 are regulated by three high-affinity serine/threonine kinase receptors, namely TβRI, TβRII and TβRIII. The renal serine protease tissue kallikrein acts on its endogenous protein substrate kininogen to form kinin peptides. The cellular actions of kinins are mediated through B 1  and B 2  G protein-coupled rhodopsin receptors. Both kinin peptides and TGF-β1 are mitogenic, and therefore may play an important role in carcinogenesis. Experiments were designed to immunolabel tissue kallikrein, TGF-β1, TβRII, TβRIII and kinin receptors using specific antibodies on serial sections of normal kidney and clear-cell renal carcinoma (CCRC) tissue, which included both the tumour and the adjacent renal parenchyma. The essential result was the localisation of tissue kallikrein, kinin B 1  and B 2  receptors and TGF-β1 primarily on the cell membranes of CCRC cells. In the distal and proximal tubules of the renal parenchyma adjacent to the carcinoma (RPTAC), immunolabelling for tissue kallikrein was reduced, but the expression of kinin B 1  and B 2  receptors was enhanced. Immunolabelling for TβRII and TβRIII was more pronounced in the proximal tubules of the tissue adjacent to the carcinoma when compared to the normal kidney. The expression of tissue kallikrein, kinin receptors, and TβRII and TβRIII may be relevant to the parenchymal invasion and metastasis of clear-cell renal carcinoma.

biological chemistry

Visualisation of transforming growth factor-β1, tissue kallikrein, and kinin and transforming growth factor-β receptors on human clear-cell renal carcinoma cells