[en] 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.
Disciplines :
Oncology
Author, co-author :
Turtoi, Andrei ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
BIANCHI, Elettra ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Maris, Pamela ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Vannozzi, R
Naccarato, Antonio Giuseppe
DELVENNE, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
De Pauw, Edwin ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Bevilacqua, G
Castronovo, Vincenzo ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
✱ These authors have contributed equally to this work.
Language :
English
Title :
Accessibilome of human glioblastoma: collagen-VI-alpha-1 is a new target and a marker of poor outcome
Alternative titles :
[en] L'analyse du protéome accessible de glioblastome identifie le collagène-VI-alpha-1 comme une nouvelle cible potentielle et un marqueur de mauvais pronostic
Publication date :
2014
Journal title :
Journal of Proteome Research
ISSN :
1535-3893
eISSN :
1535-3907
Publisher :
American Chemical Society, Washington, United States - District of Columbia
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