title: BAFF, APRIL, TWEAK, BCMA, TACI and Fn14 proteins are related to human glioma tumor grade: immunohistochemistry and public microarray data meta-analysis.
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.
authors.affiliation: Laboratories of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece ; Laboratories of Pathology, University of Crete, School of Medicine, Heraklion, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pelekanou
authors.affiliation: Laboratories of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Notas
authors.affiliation: Laboratories of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece.
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.affiliation: Laboratories of Pathology, University of Crete, School of Medicine, Heraklion, Greece.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Tsentelierou
authors.affiliation: Laboratories of Pathology, University of Crete, School of Medicine, Heraklion, Greece.
authors.forename: Efstathios N
authors.initials: EN
authors.lastname: Stathopoulos
authors.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Tsapis
authors.affiliation: Laboratories of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece.
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
mesh_terms: D053264:B-Cell Activating Factor / Q000235:genetics* / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000074049:Cytokine TWEAK; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis; D060787:Neoplasm Grading; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism; D000074050:TWEAK Receptor; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics* / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics* / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D014408:Biomarkers, Tumor; D000074049:Cytokine TWEAK; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C108467:TNFRSF13B protein, human; C086966:TNFRSF17 protein, human; C109743:TNFSF12 protein, human; C505719:TNFSF13B protein, human; D000074050:TWEAK Receptor; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D048069:Tumor Necrosis Factors