engleski

Implementation of proteomics in personalized medicine

The medicinal research is taking full advantage of recent fulminant development of the highthroughput genomic, transcriptomic, proteomic and metabolomics (“omics”) technologies. Integration of omics data and the use of bioinformatics for their evaluation and integration is the only way for decoding the basic rules that control the function of the whole organisms, by integral view to the the function of the cells, tissues and organs. This systematic approach will lead to theranostic strategy with the discovery of novel molecules as biomarkers that will pave the way to personalized medicine as the final goal. Here, se present different approaches to reach this target – use cultured cells and laboratory animals as well as the analysis of patient samples in order to study malignant modifications and discover possible disease markers. The critical molecular and cellular mechanisms involved in development, progression and metastasis of tumors remain elusive. In the rat models we demonstrated that normal prostate epithelial cells (PEC) undergo spontaneous transformation after more than 85 repeating passage steps (“high passage” p>85). This effect can be observed by the acquisition of anchorage independent growth and tumorigenicity of the cell when injected into immunodefficient mice. Minor subpopulation of these cells (SAI) had the ability to migrate through soft agar and they also showed marked differences in morphology, proliferation, motility and expression of signaling proteins as well as higher tumorigenic potential. In addition, the changes of extracellular vesicles (EV) of rat liver before and after injury were presented. Extracellular vesicles from stem- like liver epithelial cell line WB-F344, their chemically transformed lines GP7TB and GP7TB.SAI, a soft agar invasive population were investigated. Apart from changes in number, size and proteomic content, the GP7TB.SAI derived EVs significantly simulated NK-mediated cytotoxicity opposite to those purified from the less malignant GP7TB line. The information about possible communication between prostate tumor cells and possible mechanisms of bone metastasis were studied by studying changes in cell secretome and identification of proteins that can be involved in this kind of interaction. Furthermore, we investigated changes in IgG and IgM antibody glycosylation patterns in patients undergoing image guided tumor ablation. Although the glycosylation of antibodies in patients was found to vary with cancer type, discernable patterns of glycosylation change of both antibodies based on successful treatment of tumors by ablation were not identified. These findings suggest that glycosylation patterns are indicative of an immune system that is unable to prevent different types of cancer, rather than products an immunostimulatory response to the ablation and destruction of tumor itself. Present strategy opens a way for parallel determination of proteomic and glycomic changes by use of highresolution, high throughput methods, and their future use for detection of new biomarker for disease diagnosis and prognosis.

proteomics ; personalized medicine ; biomarkers

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