Overexpression of endothelin B receptor in glioblastoma: a prognostic marker and therapeutic target?
Suhas Vasaikar,
Giorgos Tsipras,
Natalia Landázuri,
Helena Costa,
Vanessa Wilhelmi,
Patrick Scicluna,
Huanhuan L. Cui,
Abdul-Aleem Mohammad,
Belghis Davoudi,
Mingmei Shang,
Sharan Ananthaseshan,
Klas Strååt,
Giuseppe Stragliotto,
Afsar Rahbar,
Kum Thong Wong,
Jesper Tegner,
Koon-Chu Yaiw,
Cecilia Söderberg-Naucler
Affiliations
Suhas Vasaikar
Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet
Giorgos Tsipras
Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet
Natalia Landázuri
Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet
Helena Costa
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet
Vanessa Wilhelmi
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet
Patrick Scicluna
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet
Huanhuan L. Cui
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet
Abdul-Aleem Mohammad
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet
Belghis Davoudi
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet
Mingmei Shang
Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet
Sharan Ananthaseshan
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet
Klas Strååt
Department of Cell and Molecular Biology, Karolinska Institutet
Giuseppe Stragliotto
Department of Neurosurgery, Karolinska University Hospital
Afsar Rahbar
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet
Kum Thong Wong
Department of Pathology
Jesper Tegner
Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet
Koon-Chu Yaiw
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet
Cecilia Söderberg-Naucler
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet
Abstract Background Glioblastoma (GBM) is the most common malignant brain tumor with median survival of 12-15 months. Owing to uncertainty in clinical outcome, additional prognostic marker(s) apart from existing markers are needed. Since overexpression of endothelin B receptor (ETBR) has been demonstrated in gliomas, we aimed to test whether ETBR is a useful prognostic marker in GBM and examine if the clinically available endothelin receptor antagonists (ERA) could be useful in the disease treatment. Methods Data from The Cancer Genome Atlas and the Gene Expression Omnibus database were analyzed to assess ETBR expression. For survival analysis, glioblastoma samples from 25 Swedish patients were immunostained for ETBR, and the findings were correlated with clinical history. The druggability of ETBR was assessed by protein-protein interaction network analysis. ERAs were analyzed for toxicity in in vitro assays with GBM and breast cancer cells. Results By bioinformatics analysis, ETBR was found to be upregulated in glioblastoma patients, and its expression levels were correlated with reduced survival. ETBR interacts with key proteins involved in cancer pathogenesis, suggesting it as a druggable target. In vitro viability assays showed that ERAs may hold promise to treat glioblastoma and breast cancer. Conclusions ETBR is overexpressed in glioblastoma and other cancers and may be a prognostic marker in glioblastoma. ERAs may be useful for treating cancer patients.
