title: TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma.
abstract: Glioma-initiating cells (GICs), also called glioma stem cells, are responsible for tumor initiation, relapse, and therapeutic resistance. Here, we show that TGF-β inhibitors, currently under clinical development, target the GIC compartment in human glioblastoma (GBM) patients. Using patient-derived specimens, we have determined the gene responses to TGF-β inhibition, which include inhibitors of DNA-binding protein (Id)-1 and -3 transcription factors. We have identified a cell population enriched for GICs that expresses high levels of CD44 and Id1 and tend to be located in a perivascular niche. The inhibition of the TGF-β pathway decreases the CD44(high)/Id1(high) GIC population through the repression of Id1 and Id3 levels, therefore inhibiting the capacity of cells to initiate tumors. High CD44 and Id1 levels confer poor prognosis in GBM patients.
authors.affiliation: Vall d'Hebron Institute of Oncology, Barcelona, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Anido
authors.forename: Andrea
authors.initials: A
authors.lastname: Sáez-Borderías
authors.forename: Alba
authors.initials: A
authors.lastname: Gonzàlez-Juncà
authors.forename: Laura
authors.initials: L
authors.lastname: Rodón
authors.forename: Gerard
authors.initials: G
authors.lastname: Folch
authors.forename: Maria A
authors.initials: MA
authors.lastname: Carmona
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Prieto-Sánchez
authors.forename: Ignasi
authors.initials: I
authors.lastname: Barba
authors.forename: Elena
authors.initials: E
authors.lastname: Martínez-Sáez
authors.forename: Ludmila
authors.initials: L
authors.lastname: Prudkin
authors.forename: Isabel
authors.initials: I
authors.lastname: Cuartas
authors.forename: Carolina
authors.initials: C
authors.lastname: Raventós
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez-Ricarte
authors.forename: M Antonia
authors.initials: MA
authors.lastname: Poca
authors.forename: David
authors.initials: D
authors.lastname: García-Dorado
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lahn
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Yingling
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodón
authors.forename: Juan
authors.initials: J
authors.lastname: Sahuquillo
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Joan
authors.initials: J
authors.lastname: Seoane
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D005909:Glioblastoma / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D051798:Inhibitor of Differentiation Protein 1 / Q000032:analysis* / Q000235:genetics; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; C075640:ID3 protein, human