Oncotarget

Research Papers:

Modulation of Dkk-3 and claudin-5 as new therapeutic strategy in the treatment of meningiomas

Maria Caffo, Emanuela Esposito, Valeria Barresi, Gerardo Caruso _, Salvatore M. Cardali, Mariagrazia Rinaldi, Raffaella Mallamace, Michela Campolo, Giovanna Casili, Alfredo Conti, Antonino Germanò, Salvatore Cuzzocrea and Letteria Minutoli

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Oncotarget. 2017; 8:68280-68290. https://doi.org/10.18632/oncotarget.20047

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Abstract

Maria Caffo1, Emanuela Esposito5, Valeria Barresi3, Gerardo Caruso1, Salvatore M. Cardali1, Mariagrazia Rinaldi2, Raffaella Mallamace4, Michela Campolo5, Giovanna Casili5, Alfredo Conti1, Antonino Germanò1, Salvatore Cuzzocrea5 and Letteria Minutoli2

1Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Unit of Neurosurgery, University of Messina, Messina, Italy

2Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

3Department of Human Pathology, University of Messina, Messina, Italy

4Unit of Anesthesia, University of Messina, Messina, Italy

5Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy

Correspondence to:

Gerardo Caruso, email: gcaruso@unime.it

Keywords: atypical meningioma, claudin-5, Dkk-3, meningioma, Wnt pathway

Received: June 03, 2017     Accepted: July 25, 2017     Published: August 07, 2017

ABSTRACT

Meningiomas are the most common tumors of the central nervous system, where the incidence is around 25% of all primary brain tumors. The optimal treatment is represented by total resection accompanied by the removal of the dura mater and bone when infiltrated by the tumor. The histological grading is the most important prognostic factor in the outcome. However, recurrences do occur in a significant proportion (10–25%) of cases, representing the most relevant clinical complication. Molecular therapies are providing to give different opportunities in the development of new treatments. The Dickkopf-related family of proteins includes four secretory proteins. The expression of the REIC/Dkk-3 gene is down-regulated in many tumor cell lines and could contribute to the immunomodulatory properties of the tissue microenvironment. An important role in carcinogenesis is played by Dickkopf protein-related protein 3, which is involved in embryonic development through its interaction and modulation of the pathway of the Wnt signal transduction. The mutations of this pathway are of clinical importance, because they lead to the onset of several cancers, including brain tumors, being also involved in tumor angiogenesis. The claudin-5, is an integral membrane protein, which regulate the permeability of the blood-brain barrier. In various pathological processes, including inflammation, trauma and tumor, claudin 5 regulate the change in endothelial or epithelial permeability, therefore, modification in claudin-5 expression may play a role in malignant transformation. The aim of our study is to demonstrate the role of Dkk-3 and claudin-5 in the pathogenesis of meningiomas. A more correct identification of the role of these proteins might suggest interesting and new molecular targets for future therapeutic protocols.


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