title: Accessibilome of human glioblastoma: collagen-VI-alpha-1 is a new target and a marker of poor outcome.
abstract: Functional targeted therapy has unfortunately failed to improve the outcome of glioblastoma patients. Success stories evidenced by the use of antibody-drug conjugates in other tumor types are encouraging, but targets specific to glioblastoma and accessible through the bloodstream remain scarce. In the current work, we have identified and characterized novel and accessible proteins using an innovative proteomic approach on six human glioblastomas; the corresponding data have been deposited in the PRIDE database identifier PXD001398. Among several clusters of uniquely expressed proteins, we highlight collagen-VI-alpha-1 (COL6A1) as a highly expressed tumor biomarker with low levels in most normal tissues. Immunohistochemical analysis of glioma samples from 61 patients demonstrated that COL6A1 is a significant and consistent feature of high-grade glioma. Deposits of COL6A1 were evidenced in the perivascular regions of the tumor-associated vasculature and in glioma cells found in pseudopalisade structures. Retrospective analysis of public gene-expression data sets from over 300 glioma patients demonstrated a significant correlation of poor patient outcome and high COL6A1 expression. In a proof-of-concept study, we use chicken chorioallantoic membrane in vivo model to show that COL6A1 is a reachable target for IV-injected antibodies. The present data warrant further development of human COL6A1 antibodies for assessing the quantitative biodistribution in the preclinical tumor models.
authors.affiliation: Metastasis Research Laboratory, GIGA-Cancer and ‡Department of Pathology, University of Liege , Bat. B23, Liege 4000, Belgium.
authors.forename: Andrei
authors.initials: A
authors.lastname: Turtoi
authors.forename: Arnaud
authors.initials: A
authors.lastname: Blomme
authors.forename: Elettra
authors.initials: E
authors.lastname: Bianchi
authors.forename: Pamela
authors.initials: P
authors.lastname: Maris
authors.forename: Riccardo
authors.initials: R
authors.lastname: Vannozzi
authors.forename: Antonio Giuseppe
authors.initials: AG
authors.lastname: Naccarato
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.forename: Edwin
authors.initials: E
authors.lastname: De Pauw
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: Vincent
authors.initials: V
authors.lastname: Castronovo
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D024142:Collagen Type VI / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008856:Microscopy, Fluorescence; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; C553839:Col6a1 protein, human; D024142:Collagen Type VI
keywords: angiogenesis; biomarkers; perivascular; survival; targeted therapy