Promising targets in renal cell cancer: Met and ron-beta

Abstract

20119 Background: The activation of Tyrosin Kinase Receptors (RTKs) produces several effects about cellular response. These are membrane receptors that bind differentiation signals, grow factors and cellular mediators. The interaction with their ligand causes the phosphorilation and internalization in the endosome. By a metabolic way, these receptors are degradated into the proteasome to small peptides that are expressed over the cellular surface joined to MHC class I mollecules, getting a better immunogenic recognition of the tumor cells. It is known that the bigger expression of the tyrosin kinase receptors in tumors is associated with an aggressive phenotype. For example overexpression of ephA2 or EGFR. Our study is based in the demostration of the overexpression of other receptors in renal cell cancer, a tumour with a disappointing response with treatment in advanced stages. On this way we can use them as targets for monoclonal antibodies and for citotoxic lymphocites CD8 stimulated that will join to peptides presented in MHC class I after the proteasomic degradation. Methods: We use Western-Blot for identifying the overexpressed RTKs in relation to normal tissue and as a reference the expression of beta-actin, that is present in every cells. The cells are from 5 murine renal cell cancer lines, (thanks to Hillman Cancer Center Institute, University of Pittsburgh. Pennsylvania. USA). The control is a murine cell line that is very similar to normal renal tissue (HK). We calculate the ratio of expression compared with the expression of normal tissue with an statistical analysis. Results: HER-2, VEGFR-2, Met, Ron-beta are overexpresed in renal cell cancer in a murine model, as EGFR (epidermic growing factor receptor). Conclusions: Met may be excellent therapeutic and inmunologic target and in selected cases of renal cell cancer. It’s known that EGFR and VEGFR are also good targets. Future research about these targets will get new options of combined immunotherapy (vaccines and monoclonal antibodies). No significant financial relationships to disclose.