Transforming growth factor-beta 1 (TGF-beta 1) has a biphasic effect on the growth of renal epithelial cells. In transformed cells, TGF-beta 1 appears to accelerate the proliferation of malignant cells. The diverse cellular functions of TGF-beta 1 are regulated by three high-affinity serine/threonine kinase receptors, namely T beta RI, T beta RII and T beta RIII. 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, and B, G protein-coupled rhodopsin receptors. Both kinin peptides and TGF-beta 1 are mitogenic, and therefore may play an important role in carcinogenesis. Experiments were designed to immunolabel tissue kallikrein, TGF-beta 1, T beta RII, T beta RIII 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, and B, receptors and TGF-beta 1 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, and B, receptors was enhanced. Immunolabelling for T beta RII and T beta RIII 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 T beta RII and T beta RIII may be relevant to the parenchymal invasion and metastasis of clear-cell renal carcinoma.
Moodley, R., Snyman, C., Odhav, B., & Bhoola, K. (2005). Visualisation of transforming growth factor-B1, tissue kallikrein, and kinin and transforming growth factor-B receptors on human clear-cell renal carcinoma cells. Biological Chemistry, 386, 375-382. https://doi.org/10.1515/BC.2005.045