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TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion

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. Iden...

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Autores principales: Porčnik, Andrej, Novak, Metka, Breznik, Barbara, Majc, Bernarda, Hrastar, Barbara, Šamec, Neja, Zottel, Alja, Jovčevska, Ivana, Vittori, Miloš, Rotter, Ana, Komel, Radovan, Lah Turnšek, Tamara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434287/
https://www.ncbi.nlm.nih.gov/pubmed/34500575
http://dx.doi.org/10.3390/molecules26175141
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author Porčnik, Andrej
Novak, Metka
Breznik, Barbara
Majc, Bernarda
Hrastar, Barbara
Šamec, Neja
Zottel, Alja
Jovčevska, Ivana
Vittori, Miloš
Rotter, Ana
Komel, Radovan
Lah Turnšek, Tamara
author_facet Porčnik, Andrej
Novak, Metka
Breznik, Barbara
Majc, Bernarda
Hrastar, Barbara
Šamec, Neja
Zottel, Alja
Jovčevska, Ivana
Vittori, Miloš
Rotter, Ana
Komel, Radovan
Lah Turnšek, Tamara
author_sort Porčnik, Andrej
collection PubMed
description 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.
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spelling pubmed-84342872021-09-12 TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion Porčnik, Andrej Novak, Metka Breznik, Barbara Majc, Bernarda Hrastar, Barbara Šamec, Neja Zottel, Alja Jovčevska, Ivana Vittori, Miloš Rotter, Ana Komel, Radovan Lah Turnšek, Tamara Molecules Article 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. MDPI 2021-08-25 /pmc/articles/PMC8434287/ /pubmed/34500575 http://dx.doi.org/10.3390/molecules26175141 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Porčnik, Andrej
Novak, Metka
Breznik, Barbara
Majc, Bernarda
Hrastar, Barbara
Šamec, Neja
Zottel, Alja
Jovčevska, Ivana
Vittori, Miloš
Rotter, Ana
Komel, Radovan
Lah Turnšek, Tamara
TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion
title TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion
title_full TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion
title_fullStr TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion
title_full_unstemmed TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion
title_short TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion
title_sort trim28 selective nanobody reduces glioblastoma stem cell invasion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434287/
https://www.ncbi.nlm.nih.gov/pubmed/34500575
http://dx.doi.org/10.3390/molecules26175141
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