title: Detection of the TNFSF members BAFF, APRIL, TWEAK and their receptors in normal kidney and renal cell carcinomas.
abstract: In advanced renal cell carcinoma (RCC), surgery combined with systemic chemotherapy and immunotherapy have had limited effectiveness. Therapeutic modalities targeting VEGF, PDGF, and c-kit using tyrosine kinase inhibitors and m-TOR using specific biologic factors are in development. Therapeutic approaches targeting TNF-alpha have shown limited efficacy, while anti-TRAIL (TNFSF10) antibodies have shown enhanced activity. The presence and potential significance of other members of the TNFSF has not been investigated. Here, we assayed the TNFSF members APRIL, BAFF, TWEAK and their receptors (BCMA, TACI, BAFFR, Fn14) in 86 conventional type clear cell RCC, using immunohistochemistry and correlated our findings with histological data and, in a limited series, follow-up of patients. We observed a differential expression of these TNFSF ligands and receptors in cancerous and non-cancerous structures. BAFF was found in all RCC; APRIL expression is associated with an aggressive phenotype, correlating negatively with patients' disease-free survival, while TWEAK and its receptor Fn14 are heterogeneously expressed, correlating negatively with the grade and survival of RCC patients. This is the first study, presenting together the TNFSF members APRIL, BAFF, TWEAK and their receptors in different areas of normal renal tissue and RCC, suggesting a potential role of these TNFSF members in renal tumor biology.
authors.affiliation: Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pelekanou
authors.forename: George
authors.initials: G
authors.lastname: Notas
authors.forename: Katerina
authors.initials: K
authors.lastname: Theodoropoulou
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Takos
authors.forename: Vassilia-Ismini
authors.initials: VI
authors.lastname: Alexaki
authors.forename: Jelena
authors.initials: J
authors.lastname: Radojicic
authors.forename: Frank
authors.initials: F
authors.lastname: Sofras
authors.forename: Andreas
authors.initials: A
authors.lastname: Tsapis
authors.forename: Efstathios N
authors.initials: EN
authors.lastname: Stathopoulos
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
mesh_terms: D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000378:metabolism*; D053301:B-Cell Maturation Antigen / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000074049:Cytokine TWEAK; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D000074050:TWEAK Receptor; 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; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D000074049:Cytokine TWEAK; D008024:Ligands; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C435926:TNFRSF13C protein, human; C086966:TNFRSF17 protein, human; C109743:TNFSF12 protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D000074050:TWEAK Receptor; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D048069:Tumor Necrosis Factors