Insulin and insulin-like growth factors act as renal cell cancer intratumoral regulators

The risk of renal cell carcinoma development is correlated with obesity and type II diabetes. Since insulin and insulin-like growth factors play a key role during development of both metabolic diseases, these molecules may be important in RCC pathophysiology We investigated the effect of insulin and IGFs on RCC cells using in vitro model with 786-O, 769-P, Caki-1, Caki-2, ACHN cancer cell lines. Cancer cells were compared with normal kidney cells - PCS-400-010 and HEK293. The growth, viability of cells as well as migration rate were assessed upon hormonal stimulation. The insulin receptor and Insulin-like growth factor 1 receptor presence were evaluated and the expression of 84 genes related to insulin signaling pathway. In all RCC cell lines IGF-1R expression was confirmed in contrast to IR, which was expressed only in control HEK293 cell line. Insulin and IGFs stimulated RCC cells growth and migration rate. Insulin, IGF-1 and IGF-2 triggered both IR and IGF-1R phosphorylation. Analyzed RCC did not secret insulin, IGF-1 or IGF-2 and were not activated in autocrine-paracrine signaling loop. Insulin and IGFs stimulations triggered down-regulation of PI3K-Akt-mTOR and Ras-MAPK pathway gens, as well as DOK2-3, INS, FRS3, IRS1-2, IGF1R - genes encoding insulin receptor-associated proteins. In conclusion, we showed that IGFs and insulin may play a stimulatory role for renal cancer cells, thus they can possibly affect renal cancer tumorigenesis and progression on cellular level.