title: APO010, a synthetic hexameric CD95 ligand, induces death of human glioblastoma stem-like cells.
abstract: The treatment of glioblastoma remains a major challenge in the field of neuro-oncology. There is emerging evidence that glioblastomas consist of heterogeneous cell populations with a small subset of cells with stem cell-like properties which might be resistant to conventional therapy and are thus crucial for tumor recurrence. These glioma-initiating cells (GICs) are therefore an attractive therapeutic target. Death receptor activation is one promising approach of cancer therapy. The synthetic hexameric cluster of differentiation 95 (CD95) agonist APO010 exhibits strong antiglioma activity towards human glioma cell lines, as well as in cell cultures of primary glioblastoma. Here, we investigated the ability of APO010 to induce cell death in a panel of previously well-defined GIC lines. The GIC lines and their derived differentiated cultures expressed CD95 on the cell surface and were sensitive towards APO010-mediated cell death to a variable extent. Temozolomide enhanced sensitivity of GICs to APO010. APO010 warrants being further evaluated as a tool to target GICs.
authors.affiliation: Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland. guenter.eisele@usz.ch.
authors.forename: Günter
authors.initials: G
authors.lastname: Eisele
authors.forename: Fabian
authors.initials: F
authors.lastname: Wolpert
authors.forename: Guillaume
authors.initials: G
authors.lastname: Decrey
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000276:immunology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000378:metabolism*; D005909:Glioblastoma / Q000276:immunology / Q000473:pathology*; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology*; D010455:Peptides / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D000077204:Temozolomide
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018906:Antineoplastic Agents, Alkylating; D053222:Fas Ligand Protein; D006023:Glycoproteins; C558004:Mega-Fas-ligand; D010455:Peptides; D011993:Recombinant Fusion Proteins; D003606:Dacarbazine; D000077204:Temozolomide
keywords: CD95 ligand; Glioma stem cell; apoptosis; temozolomide