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Oncotarget. 2017 Apr 21;8(34):56243-56254. doi: 10.18632/oncotarget.17353. eCollection 2017 Aug 22.

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

Author information

1
Department of Internal Medicine V, Hematology and Medical Oncology, Innsbruck Medical University, Innsbruck, Austria.
2
Laboratory for Tumor Biology and Angiogenesis, Innsbruck Medical University, Innsbruck, Austria.
3
Tyrolean Cancer Research Institute, Innsbruck, Austria.
4
Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
5
Department of Hemato-Oncology, University Hospital Ostrava, Ostrava, Czech Republic.
6
Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria.
#
Contributed equally

Abstract

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.

KEYWORDS:

ELISA; GRP78; MGUS; multiple myeloma; prognostic marker

Conflict of interest statement

CONFLICTS OF INTEREST The research leading to these results has received funding from the Seventh Framework Program (FP7/2007-2013) under grant agreement n°278570” (OPTATIO).

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