BAFF, APRIL, TWEAK, BCMA, TACI and Fn14 proteins are related to human glioma tumor grade: immunohistochemistry and public microarray data meta-analysis

Vassiliki Pelekanou; George Notas; Marilena Kampa; Eleftheria Tsentelierou; Efstathios N Stathopoulos; Andreas Tsapis; Elias Castanas

doi:10.1371/journal.pone.0083250

BAFF, APRIL, TWEAK, BCMA, TACI and Fn14 proteins are related to human glioma tumor grade: immunohistochemistry and public microarray data meta-analysis

PLoS One. 2013 Dec 20;8(12):e83250. doi: 10.1371/journal.pone.0083250. eCollection 2013.

Authors

Vassiliki Pelekanou¹, George Notas², Marilena Kampa², Eleftheria Tsentelierou³, Efstathios N Stathopoulos³, Andreas Tsapis⁴, Elias Castanas²

Affiliations

¹ Laboratories of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece ; Laboratories of Pathology, University of Crete, School of Medicine, Heraklion, Greece.
² Laboratories of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece.
³ Laboratories of Pathology, University of Crete, School of Medicine, Heraklion, Greece.
⁴ Laboratories of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece ; INSERM U976, Hôpital Saint Louis, Paris, France; (4) Université Paris Diderot, Paris, France.

Abstract

Gliomas are common and lethal tumors of the central nervous system (CNS). Genetic alterations, inflammatory and angiogenic processes have been identified throughout tumor progression; however, treatment still remains palliative for most cases. Biological research on parameters influencing cell survival, invasion and tumor heterogeneity identified several cytokines interfering in CNS inflammation, oxidative stress and malignant transformation, including TNF-superfamily (TNFSF) members. In this report we performed a meta-analysis of public gene-array data on the expression of a group of TNFSF ligands (BAFF, APRIL, TWEAK) and their receptors (BAFF-R, TACI, BCMA, Fn14) in gliomas. In addition, we investigated by immunohistochemistry (IHC) the tumor cells' expression of these ligands and receptors in a series of 56 gliomas of different grade. We show that in IHC, BAFF and APRIL as well as their cognate receptors (BCMA, TACI) and Fn14 expression correlate with tumor grade. This result was not evidenced in micro-arrays meta-analysis. Finally, we detected for the first time Fn14, BAFF, BCMA and TACI in glioma-related vascular endothelium. Our data, combined with our previous report in glioma cell lines, suggest a role for these receptors and ligands in glioma biology and advance these molecules as potential markers for the classification of these tumors to the proliferative, angiogenic or stem-like molecular subtype.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

B-Cell Activating Factor / genetics*
B-Cell Activating Factor / metabolism
B-Cell Maturation Antigen / genetics*
B-Cell Maturation Antigen / metabolism
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Central Nervous System Neoplasms / genetics*
Central Nervous System Neoplasms / metabolism
Central Nervous System Neoplasms / pathology
Cytokine TWEAK
Endothelium, Vascular / metabolism
Endothelium, Vascular / pathology
Gene Expression Regulation, Neoplastic
Glioma / genetics*
Glioma / metabolism
Glioma / pathology
Humans
Immunohistochemistry
Microarray Analysis
Neoplasm Grading
Receptors, Tumor Necrosis Factor / genetics*
Receptors, Tumor Necrosis Factor / metabolism
TWEAK Receptor
Transmembrane Activator and CAML Interactor Protein / genetics*
Transmembrane Activator and CAML Interactor Protein / metabolism
Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics*
Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism
Tumor Necrosis Factors / genetics*
Tumor Necrosis Factors / metabolism

Substances

B-Cell Activating Factor
B-Cell Maturation Antigen
Biomarkers, Tumor
Cytokine TWEAK
Receptors, Tumor Necrosis Factor
TNFRSF12A protein, human
TNFRSF13B protein, human
TNFRSF17 protein, human
TNFSF12 protein, human
TNFSF13B protein, human
TWEAK Receptor
Transmembrane Activator and CAML Interactor Protein
Tumor Necrosis Factor Ligand Superfamily Member 13
Tumor Necrosis Factors

Grants and funding

This work was partially supported by the European Union-FP7 Marie Curie Actions-Career Reintegration Grants PCIG-GA-2011-303723 (to VP) and the University of Crete Research Committee funds to EC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.