TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion.


Journal

Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009

Informations de publication

Date de publication:
25 Aug 2021
Historique:
received: 06 07 2021
revised: 22 08 2021
accepted: 23 08 2021
entrez: 10 9 2021
pubmed: 11 9 2021
medline: 29 9 2021
Statut: epublish

Résumé

Glioblastoma (GB), is the most common and aggressive malignant primary brain tumour in adults. Intra- and inter-tumour heterogeneity, infiltrative GB cell invasion and presence of therapy-resistant GB stem cells (GSCs) represent major obstacles to favourable prognosis and poor therapy response. Identifying the biomarkers of the most aggressive tumour cells and their more efficient targeting strategies are; therefore, crucial. Recently, transcription factor TRIM28 has been identified as a GB biomarker and, in this study, we have shown high expression of TRIM28 in GB and in low grade gliomas as well as higher expression in GSCs vs. differentiated GB cells, although in both cases not significant. We demonstrated significant in vitro inhibition of GB cells and GSCs invasiveness and spread in zebrafish brains in vivo by anti-TRIM28 selective nanobody NB237. TRIM28 was also enriched in GB (tumour) core and associated with the expression of stem cell genes, but was not prognostic for overall survival. However, based on the above results, we conclude that TRIM28 nanobody NB237 offers a new opportunity as a GB therapeutic tool.

Identifiants

pubmed: 34500575
pii: molecules26175141
doi: 10.3390/molecules26175141
pmc: PMC8434287
pii:
doi:

Substances chimiques

TRIM28 protein, human EC 2.3.2.27
Tripartite Motif-Containing Protein 28 EC 2.3.2.27

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Javna Agencija za Raziskovalno Dejavnost RS
ID : Grant Program P1-0245 to TLT
Organisme : Javna Agencija za Raziskovalno Dejavnost RS
ID : post-doctoral projects Z3-1870 to BB
Organisme : Javna Agencija za Raziskovalno Dejavnost RS
ID : post-doctoral projects Z3-1869 to IJ
Organisme : Javna Agencija za Raziskovalno Dejavnost RS
ID : post-doctoral projects Z3-2649 to NŠ
Organisme : European Program of Cross-Border Cooperation for Slovenia-Italy Interreg
ID : TRANS-GLIOMA to TLT, RK

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Auteurs

Andrej Porčnik (A)

Department of Neurosurgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.

Metka Novak (M)

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia.

Barbara Breznik (B)

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia.

Bernarda Majc (B)

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia.
Jožef Stefan International Postgraduate School, 1000 Ljubljana, Slovenia.

Barbara Hrastar (B)

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia.

Neja Šamec (N)

Medical Centre for Molecular Biology, Institute for Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.

Alja Zottel (A)

Medical Centre for Molecular Biology, Institute for Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.

Ivana Jovčevska (I)

Medical Centre for Molecular Biology, Institute for Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.

Miloš Vittori (M)

Department of Biology, Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia.

Ana Rotter (A)

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia.

Radovan Komel (R)

Medical Centre for Molecular Biology, Institute for Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.

Tamara Lah Turnšek (T)

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia.
Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia.

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Classifications MeSH