Borjan Bojana,

University / Clinic: Department of Internal Medicine
Institute: Division of Haematology and Oncology
Research Area: Tumor Biology and Angiogenesis


  Funded by: FWF

Research Topic:
GRP78 in tumor resistance
Cancer cells and their microenvironment adapt to genotoxic stress by induction of the GRP-78/BiP (glucose-regulated protein 78/immunoglobulin heavy chain binding protein) a chaperone protein of the endoplasmatic reticulum with antiapoptotic properties. In particular GRP78 expression is elevated in tumor cells that grow in a microenvironment characterized by glucose deprivation, acidosis and hypoxia, i.e. in viable tumor cells bordering necrotic regions created by therapy. These cells generally are highly chemoresistant and protected against lysis by cytotoxic T-cells. Moreover, highly metastatic cells express GRP78 ectopically on the cell surface making cells insensitive to TGF beta signaling. In human cancers elevated GRP78 expression generally correlates with higher pathological grade, recurrence and poor patient survival in breast, prostate and colon cancer. Hitherto, effects of GRP78 exposed on the cell surface or released by tumor cells are poorly understood in context to the respective microenvironment, i.e. immune resistance and resistance to anti-angiogenic drugs. Based on our previous work on the role of tumor-derived GRP78 on anti-angiogenic therapies (Kern et al, 2009) we plan to perform detailed and novel investigations within this research consortium, to gain a profound knowledge on the role of GRP78 in intrinsic and extrinsic tumor resistance of solid and hematological tumors topshop
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Selected publications: