Extracellular LGALS3BP: a potential disease marker and actionable target for antibody-drug conjugate therapy in glioblastoma.
Mol Oncol
; 17(8): 1460-1473, 2023 08.
Article
en En
| MEDLINE
| ID: mdl-37195369
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
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Glioblastoma
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Inmunoconjugados
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Vesículas Extracelulares
Tipo de estudio:
Diagnostic_studies
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Screening_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Mol Oncol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2023
Tipo del documento:
Article
País de afiliación:
Italia