title: Liposome-bound TRAIL induces superior DR5 clustering and enhanced DISC recruitment in histiocytic lymphoma U937 cells.
abstract: Human Apo2-Ligand/TRAIL is a promising antitumor agent. Our group demonstrated that TRAIL was physiologically released to the extracellular medium inserted in lipid vesicles, known as exosomes. Recently we demonstrated that artificial lipid nanoparticles coated with bioactive TRAIL (LUV-TRAIL), which resemble the natural exosomes, greatly improved TRAIL activity compared with the soluble form of this death ligand and were able to induce apoptosis in hematological malignancies. In this study we have deepened the underlying mechanism of action of LUV-TRAIL in hematologic cells. Using histiocytic lymphoma U937 cells, we demonstrated that TRAIL signaling almost exclusively depends on DR5 despite these cells expressing high amounts of DR4, and proved that LUV-TRAIL's higher pro-apoptotic effect relies on its superior ability to induce DR5 clustering on cell surface, therefore enhancing DISC recruitment and triggering caspase activation more efficiently than the soluble form of TRAIL.
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Spain. Electronic address: diego_demiguel@hotmail.com.
authors.forename: Diego
authors.initials: D
authors.lastname: De Miguel
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Spain. Electronic address: annaiss89@hotmail.com.
authors.forename: Ana
authors.initials: A
authors.lastname: Gallego-Lleyda
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Spain. Electronic address: anel@unizar.es.
authors.forename: Alberto
authors.initials: A
authors.lastname: Anel
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Spain; Instituto de Nanociencia de Aragón, Spain. Electronic address: lumartin@unizar.es.
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez-Lostao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053418:Death Domain Receptor Signaling Adaptor Proteins; D006801:Humans; D008081:Liposomes; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D053418:Death Domain Receptor Signaling Adaptor Proteins; D008081:Liposomes; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human
keywords: Caspase; DISC; DR5; Leukemia; Liposome; TRAIL