Functional intactness of stimulatory and inhibitory autocrine loops in human renal carcinoma cell lines of the clear cell type.

U Ramp, K Jaquet, P Reinecke, C Schardt, U Friebe, T Nitsch, N Marx, H E Gabbert, C D Gerharz

Institute of Pathology, University of Düsseldorf, Germany.

The Journal of urology 1997 Jun

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The aim of the present study was to analyze the contribution of different stimulatory and inhibitory growth factors to the deregulated proliferation of human RCCs. The expression of different growth factors and their corresponding receptors were analyzed by Northern blot, FACS, ELISA and immunocytochemistry in 13 permanent human RCC cell lines of the clear cell type. Moreover, the functional intactness of growth factor-related signal transduction pathways was investigated. All RCC cell lines expressed EGF-receptor mRNA and protein and 10 cell lines secreted TGF-alpha. Exogeneously added TGF-alpha resulted in a significant (p < 0.05) stimulation of growth in 6 RCC cell lines and a significant (p < 0.05) inhibition of proliferation in 3 cell lines. PDGF B and the corresponding type beta receptor were expressed in a single cell line. mRNA expression of PDGF A and PDGF-alpha-receptor as well as IGF-1 and its receptor could not be detected in any cell line. Eleven RCC cell lines expressed TGF-beta 1 mRNA and in all cell lines TGF-beta 1 secretion into the supernatant could be demonstrated. Whereas all cell lines exhibited TGF-beta type II-receptor mRNA, type I-receptor mRNA could be detected only in 3 cell lines. TGF-beta type III-receptor was observed in 1 cell line. Exogeneously added TGF-beta1 resulted in a significant (p < 0.05) inhibition of proliferation in 7 RCC cell lines. Clear cell RCCs exhibit a complex and heterogeneous expression pattern for various growth factors and their receptors. Growth factor secretion and intact signal transduction pathways in most clear cell RCCs facilitate an intricate modulation of RCC growth by autocrine and paracrine interactions between tumor cells and host tissue.

Citation

U Ramp, K Jaquet, P Reinecke, C Schardt, U Friebe, T Nitsch, N Marx, H E Gabbert, C D Gerharz. Functional intactness of stimulatory and inhibitory autocrine loops in human renal carcinoma cell lines of the clear cell type. The Journal of urology. 1997 Jun;157(6):2345-50