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Expression and release of glucose-regulated protein-78 (GRP78) in multiple myeloma

N. Steiner, B. Borjan, R. Hajek, K. Jöhrer, G. Göbel, W. Willenbacher, J. Kern, E. Gunsilius, G. Untergasser,

. 2017 ; 8 (34) : 56243-56254. [pub] 20170421

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc17031950

INTRODUCTION: Multiple myeloma (MM) is a plasma cell neoplasm that is mostly incurable due to acquired resistance during the treatment course. Thus, we evaluated expression and release of glucose-regulated protein 78 kDa (GRP78/BiP), an endoplasmic reticulum (ER) based pro-survival chaperone involved in immunoglobulin folding and unfolded protein responses. RESULTS: GRP78 protein expression in the ER and on the cell surface did not significantly differ between MGUS, NDMM and RRMM patients although there was a trend to higher surface expression in RRMM. In bone marrow plasma, the amount of released GRP78 protein was not significantly increased between MGUS-, NDMM- and RRMM patients. MM cells of the three cell lines release GRP78 as full-length protein under apoptotic, but not under acidotic or ER-stress conditions. In necrosis, only proteolytic fragments of GRP78 were detected in supernatants of MM cells. MATERIALS AND METHODS: GRP78 protein expression and plasma levels were quantified in bone marrow aspirates of patients with monoclonal gammopathy of undetermined significance (MGUS, n = 29), newly diagnosed MM (NDMM, n = 29) and with relapsed/refractory MM (RRMM, n = 15) by immunohistochemistry and sandwich ELISA. The human MM cell lines U266, NCI-H929 and OPM-2 were used for functional GRP78 release- and processing studies after induction of acidosis, ER stress, apoptosis and necrosis. CONCLUSIONS: Ectopic expression of GRP78 on cell membrane or its release in the microenvironment is not a suitable marker to distinguish MGUS from NDMM and RRMM.

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$a INTRODUCTION: Multiple myeloma (MM) is a plasma cell neoplasm that is mostly incurable due to acquired resistance during the treatment course. Thus, we evaluated expression and release of glucose-regulated protein 78 kDa (GRP78/BiP), an endoplasmic reticulum (ER) based pro-survival chaperone involved in immunoglobulin folding and unfolded protein responses. RESULTS: GRP78 protein expression in the ER and on the cell surface did not significantly differ between MGUS, NDMM and RRMM patients although there was a trend to higher surface expression in RRMM. In bone marrow plasma, the amount of released GRP78 protein was not significantly increased between MGUS-, NDMM- and RRMM patients. MM cells of the three cell lines release GRP78 as full-length protein under apoptotic, but not under acidotic or ER-stress conditions. In necrosis, only proteolytic fragments of GRP78 were detected in supernatants of MM cells. MATERIALS AND METHODS: GRP78 protein expression and plasma levels were quantified in bone marrow aspirates of patients with monoclonal gammopathy of undetermined significance (MGUS, n = 29), newly diagnosed MM (NDMM, n = 29) and with relapsed/refractory MM (RRMM, n = 15) by immunohistochemistry and sandwich ELISA. The human MM cell lines U266, NCI-H929 and OPM-2 were used for functional GRP78 release- and processing studies after induction of acidosis, ER stress, apoptosis and necrosis. CONCLUSIONS: Ectopic expression of GRP78 on cell membrane or its release in the microenvironment is not a suitable marker to distinguish MGUS from NDMM and RRMM.
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$a Borjan, Bojana $u Laboratory for Tumor Biology and Angiogenesis, Innsbruck Medical University, Innsbruck, Austria. Tyrolean Cancer Research Institute, Innsbruck, Austria.
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$a Hajek, Roman $u Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic. Department of Hemato-Oncology, University Hospital Ostrava, Ostrava, Czech Republic.
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$a Jöhrer, Karin $u Tyrolean Cancer Research Institute, Innsbruck, Austria.
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$a Göbel, Georg $u Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria.
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$a Willenbacher, Wolfgang $u Department of Internal Medicine V, Hematology and Medical Oncology, Innsbruck Medical University, Innsbruck, Austria.
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$a Kern, Johann $u Tyrolean Cancer Research Institute, Innsbruck, Austria.
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$a Gunsilius, Eberhard $u Department of Internal Medicine V, Hematology and Medical Oncology, Innsbruck Medical University, Innsbruck, Austria. Laboratory for Tumor Biology and Angiogenesis, Innsbruck Medical University, Innsbruck, Austria.
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$a Untergasser, Gerold $u Department of Internal Medicine V, Hematology and Medical Oncology, Innsbruck Medical University, Innsbruck, Austria. Tyrolean Cancer Research Institute, Innsbruck, Austria.
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