title: Tumor-derived endothelial cells evade apoptotic activity of the interferon-inducible IFI16 gene.
abstract: The human interferon (IFN)-inducible IFI16 protein is a member of the 200-amino acid repeat family encoded by the HIN-200 genes. Forced IFI16 expression in normal human endothelial cells (ECs) inhibits cell growth and tube morphogenesis of ECs through the triggering of apoptosis by caspase-2 and caspase-3 via nuclear factor-κB (NF-κB) complex activation. Accumulating evidence suggests that tumor-derived ECs (TECs) possess a distinct and unique phenotype compared with normal ECs, and they may be able to acquire resistance to antiangiogenic agents such as IFNs. However, few functional studies are available on cultured TEC. In the present study, we have demonstrated that TEC obtained from tumors of various histological origin, namely kidney (Eck25), breast (B-TEC), and head and neck (HN4), continued to proliferate and generate microtubules on Matrigel following IFI16 overexpression. In contrast to normal ECs, they were resistant to apoptosis triggered by caspase-2 and caspase-3 activation via the NF-κB complex. At the molecular level, when overexpressed in TEC, IFI16 appeared unable to regulate NF-κB activity and lead to caspase activation. Altogether, these results indicate that TECs display abnormal responses, in terms of survival and angiogenic properties, to an antiproliferative and antiangiogenic IFN-inducible gene such as IFI16.
authors.affiliation: Department of Public Health and Microbiology, Medical School, University of Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gugliesi
authors.forename: Valentina
authors.initials: V
authors.lastname: Dell'oste
authors.forename: Marco
authors.initials: M
authors.lastname: De Andrea
authors.forename: Rossella
authors.initials: R
authors.lastname: Baggetta
authors.forename: Michele
authors.initials: M
authors.lastname: Mondini
authors.forename: Claudia
authors.initials: C
authors.lastname: Zannetti
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bussolati
authors.forename: Gianni
authors.initials: G
authors.lastname: Camussi
authors.forename: Marisa
authors.initials: M
authors.lastname: Gariglio
authors.forename: Santo
authors.initials: S
authors.lastname: Landolfo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D048708:Cell Growth Processes / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D057131:Immune Evasion; D007372:Interferons / Q000494:pharmacology / Q000627:therapeutic use*; D009024:Morphogenesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D016328:NF-kappa B; D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human; D007372:Interferons; D053148:Caspase 3