Extracellular LGALS3BP: a potential disease marker and actionable target for antibody-drug conjugate therapy in glioblastoma.
LGALS3BP
antibody-drug conjugates
extracellular vesicles
glioblastoma
liquid biopsy
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
14
04
2023
received:
11
01
2023
accepted:
16
05
2023
medline:
4
8
2023
pubmed:
17
5
2023
entrez:
17
5
2023
Statut:
ppublish
Résumé
Glioblastoma multiforme (GBM) is a lethal disease characterized by an overall survival of about 1 year, making it one of the most aggressive tumours, with very limited therapeutic possibilities. Specific biomarkers for early diagnosis as well as innovative therapeutic strategies are urgently needed to improve the management of this deadly disease. In this work, we demonstrated that vesicular galectin-3-binding protein (LGALS3BP), a glycosylated protein overexpressed in a variety of human malignancies, is a potential GBM disease marker and can be efficiently targeted by a specific antibody-drug conjugate (ADC). Immunohistochemical analysis on patient tissues showed that LGALS3BP is highly expressed in GBM and, compared with healthy donors, the amount of vesicular but not total circulating protein is increased. Moreover, analysis of plasma-derived extracellular vesicles from mice harbouring human GBM revealed that LGALS3BP can be used for liquid biopsy as a marker of disease. Finally, an ADC targeting LGALS3BP, named 1959-sss/DM4, specifically accumulates in tumour tissue, producing a potent and dose-dependent antitumor activity. In conclusion, our work provides evidence that vesicular LGALS3BP is a potential novel GBM diagnostic biomarker and therapeutic target deserving further preclinical and clinical validation.
Identifiants
pubmed: 37195369
doi: 10.1002/1878-0261.13453
pmc: PMC10399712
doi:
Substances chimiques
Biomarkers, Tumor
0
Immunoconjugates
0
LGALS3BP protein, human
0
Antigens, Neoplasm
0
Banques de données
RefSeq
['NM_005567.4']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1460-1473Informations de copyright
© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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