The sigma-1 receptor: Potential role in the modulation of cellular radiation sensitivity

Article type: Research Article

Authors: Belter, Birgit^{a; 1} | Deuther-Conrad, Winnie^{b; 1} | Hofheinz, Frank^c | Neuber, Christin^a | Bachmann, Michael^{d; e; f; g} | Brust, Peter^b | Pietzsch, Jens^{a; h; *}

Affiliations: [a] Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Department of Radiopharmaceutical and Chemical Biology, Dresden, Germany | [b] Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Department Neuroradiopharmaceuticals, Leipzig, Germany | [c] Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Department Positron Emission Tomography, Dresden, Germany | [d] Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Department of Radioimmunology, Dresden, Germany | [e] Technische Universität Dresden, University Hospital Carl Gustav Carus, University Cancer Center (UCC), Tumor Immunology, Dresden, Germany | [f] Technische Universität Dresden, University Hospital Carl Gustav Carus, National Center for Tumor Diseases (NCT), Dresden, Germany | [g] German Cancer Consortium (DKTK), Partner Site Dresden, Dresden, Germany | [h] Technische Universität Dresden, School of Science, Faculty of Chemistry and Food Chemistry, Dresden, Germany

Correspondence: [*] Corresponding author: Prof. Dr. Jens Pietzsch, Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Bautzner Landstrasse 400, 01328 Dresden, Germany. E-mail: [email protected].

Note: [1] B.B. and W.D-C. contributed equally.

Abstract: Direct interaction of the sigma-1 (σ1) receptor, an endoplasmic reticulum chaperone located in close vicinity to the mitochondrion, with a variety of proteins involved in essential processes regulating proliferation, survival, and death of cells, indicates a role of this protein in tumor biology. Since tumor therapies address precisely these processes to stop the growth of tumor cells, the σ1 receptor could be a suitable modulator of the effectiveness of selected therapies. Recent initial studies have shown not only anti-proliferative effects of ligands targeting this protein, but also modulating effects in both chemotherapy and radiotherapy. However, in this regard the influence of functional expression of the σ1receptor has not yet been fully clarified. The purpose of this pilot experiment was to investigate the role of σ1 receptor on cellular radiosensitivity in an in vitro model. Therefore, clonogenic assays were performed to assess the susceptibility of HEK293 cells, stably transfected with human σ1 receptor, towards irradiation (X-ray) in comparison to non-transfected cells. Moreover, irradiation combined with pharmacological treatment should prove whether agonistic and antagonistic ligand binding to σ1 receptor influences the effectiveness of radiation treatment. The data obtained are not fully conclusive by indicating, on the one hand, an involvement of σ1 receptor in radiation-induced effects along with pharmacological effects independent from the σ1 receptor level, on the other hand, suggesting limitations of the model used herein. Consequently, subsequent work will focus on the investigation of tumor cells with different receptor densities.

Keywords: Chaperone protein, clonogenic assay, endoplasmatic reticulum, intracellular transmembrane receptors, radio resistance, sigma-1 receptor ligands

DOI: 10.3233/JCB-209007

Journal: Journal of Cellular Biotechnology, vol. 6, no. 1, pp. 13-21, 2020