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The expression of HMGB1 protein and its receptor RAGE in human malignant tumors

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Abstract

High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein discovered to be released in the extracellular medium as a response to various stimuli and implicated in cancerogenesis. High HMGB1 levels are reported in a variety of tumor types, but there are few data relating HMGB1 to the histological grade or to a particular cell type and cellular localization. We studied the expression of HMGB1 protein in malignant human tumors of different differentiation level and in tumor metastasis. In all tumor tissues, the protein level is elevated. In moderately differentiated carcinomas, the localization of the protein is perinuclear, while in the low differentiated; there is a tendency for non-specific nuclear localization. HMGB1 protein and its receptor RAGE are identified as a ligand–receptor pair that plays an important role in regulating the invasiveness of tumor cells. RAGE is not produced in all of the tested tumor specimens. We found high level of expression in hepatocellular, colorectal, and breast cribriform carcinomas, but not in malignant testicular specimens. Probably, the RAGE synthesis is related to distinctive tumor types. In metastatic cells, RAGE exhibits higher level of expression losing its specific granular cytosolic pattern characteristic for the primary tumors.

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Acknowledgments

We thank Dr. Gulubova and Dr. Vlaykova from the Medical Faculty, Tracian University, and Stara Zagora for the surgical specimens and fruitful advices. This study was supported by grant CRP/BUL 06-01 from International Centre for Genetic Engineering and Biotechnology.

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  1. Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

    Nora Kostova, Stanislava Zlateva, Iva Ugrinova & Evdokia Pasheva

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  1. Nora Kostova
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  2. Stanislava Zlateva
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  4. Evdokia Pasheva
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Correspondence to Evdokia Pasheva.

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Kostova, N., Zlateva, S., Ugrinova, I. et al. The expression of HMGB1 protein and its receptor RAGE in human malignant tumors. Mol Cell Biochem 337, 251–258 (2010). https://doi.org/10.1007/s11010-009-0305-0

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