The Na, K-ATPase β-Subunit Isoforms Expression in Glioblastoma Multiforme: Moonlighting Roles.

Deborah Rotoli, Mariana-Mayela Cejas, María-Del-Carmen Maeso, Natalia-Dolores Pérez-Rodríguez, Manuel Morales, Julio Ávila, Ali Mobasheri, Pablo Martín-Vasallo

Journal: International journal of molecular sciences 2018;18(11):2369

PMID: 29117147

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Abstract

Glioblastoma multiforme (GBM) is the most common form of malignant glioma. Recent studies point out that gliomas exploit ion channels and transporters, including Na, K-ATPase, to sustain their singular growth and invasion as they invade the brain parenchyma. Moreover, the different isoforms of the β-subunit of Na, K-ATPase have been implicated in regulating cellular dynamics, particularly during cancer progression. The aim of this study was to determine the Na, K-ATPase β subunit isoform subcellular expression patterns in all cell types responsible for microenvironment heterogeneity of GBM using immunohistochemical analysis. All three isoforms, β1, β2/AMOG (Adhesion Molecule On Glia) and β3, were found to be expressed in GBM samples. Generally, β1 isoform was not expressed by astrocytes, in both primary and secondary GBM, although other cell types (endothelial cells, pericytes, telocytes, macrophages) did express this isoform. β2/AMOG and β3 positive expression was observed in the cytoplasm, membrane and nuclear envelope of astrocytes and GFAP (Glial Fibrillary Acidic Protein) negative cells. Interestingly, differences in isoforms expression have been observed between primary and secondary GBM: in secondary GBM, β2 isoform expression in astrocytes was lower than that observed in primary GBM, while the expression of the β3 subunit was more intense. These changes in β subunit isoforms expression in GBM could be related to a different ionic handling, to a different relationship between astrocyte and neuron (β2/AMOG) and to changes in the moonlighting roles of Na, K-ATPase β subunits as adaptor proteins and transcription factors.

Address: Laboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular and Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, La Laguna, Av. Astrofísico Sánchez s/n, 38206 La Laguna, Tenerife, Spain. [email protected].; CNR-National Research Council, Institute of Endocrinology and Experimental Oncology (IEOS), Via Sergio Pansini, 5-80131 Naples, Italy. [email protected].; Laboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular and Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, La Laguna, Av. Astrofísico Sánchez s/n, 38206 La Laguna, Tenerife, Spain. [email protected].; Service of Pathology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Canary Islands, Spain. [email protected].; Service of Medical Oncology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Canary Islands, Spain. [email protected].; Service of Medical Oncology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Canary Islands, Spain. [email protected].; Medical Oncology, Hospiten® Hospitals, 38001 Santa Cruz de Tenerife, Tenerife, Spain. [email protected].; Laboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular and Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, La Laguna, Av. Astrofísico Sánchez s/n, 38206 La Laguna, Tenerife, Spain. [email protected].; Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK. [email protected].; Laboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular and Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, La Laguna, Av. Astrofísico Sánchez s/n, 38206 La Laguna, Tenerife, Spain. [email protected].

DOI: 10.3390/ijms18112369

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https://medlineplus.gov/braintumors.html

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https://assays.cancer.gov/CPTAC-27

MeSH Terms: Adenosine Triphosphatases, Astrocytes, Biomarkers, Tumor, Brain Neoplasms, Cation Transport Proteins, Cell Adhesion, Cell Adhesion Molecules, Neuronal, Female, Glioblastoma, Humans, Male, Neurons, Sodium-Potassium-Exchanging ATPase, Tumor Microenvironment