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Anti-vimentin nanobody decreases glioblastoma cell invasion in vitro and in vivo
ID Zottel, Alja (Author), ID Novak, Metka (Author), ID Šamec, Neja (Author), ID Majc, Bernarda (Author), ID Colja, Sara (Author), ID Katrašnik, Mojca (Author), ID Vittori, Miloš (Author), ID Hrastar, Barbara (Author), ID Rotter, Ana (Author), ID Porčnik, Andrej (Author), ID Lah Turnšek, Tamara (Author), ID Komel, Radovan (Author), ID Breznik, Barbara (Author), ID Jovchevska, Ivana (Author)

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Abstract
Purpose: Glioblastoma (GBM) is the most common primary brain tumour and one of the deadliest cancers. In addition to late diagnosis and inadequate treatment, the extremely low survival rate is also due to the lack of appropriate therapeutic biomarkers and corresponding therapeutic agents. One of the potential therapeutic biomarkers is the intermediate filament vimentin, which is associated with epithelial-mesenchymal transition (EMT). The purpose of this study was to analyse the effect of the anti-vimentin nanobody Nb79 on cell invasion in vitro and in vivo. To further our understanding of the mechanism of action, we investigated the association between Nb79 and EMT in GBM and GBM stem cells by analysing the expression levels of key EMT-related proteins. Methods: The expression of vimentin in glioma tissues and cells was determined by RT-qPCR. An invasion assay was performed on differentiated glioblastoma cell line U-87 MG and stem cell line NCH421k in vitro as well as in vivo in zebrafish embryos. The effect of Nb79 on expression of EMT biomarkers beta-catenin, vimentin, ZEB-1 and ZO1 was determined by Western blot and immunocytochemistry. Results: Our study shows that vimentin is upregulated in glioblastoma tissue compared to lower grade glioma and non-tumour brain tissue. We demonstrated that treatment with Nb79 reduced glioblastoma cell invasion by up to 64% in vitro and up to 21% in vivo. In addition, we found that the tight junction protein ZO-1 had higher expression on the cell membrane, when treated with inhibitory anti-vimentin Nb79 compared to control. Conclusion: In conclusion, our results suggest that anti-vimentin nanobody Nb79 is a promising tool to target glioblastoma cell invasion.

Language:English
Keywords:glioblastoma, vimentin, nanobody, invasion, EMT
Work type:Article
Typology:1.01 - Original Scientific Article
Organization:MF - Faculty of Medicine
BF - Biotechnical Faculty
FKKT - Faculty of Chemistry and Chemical Technology
Publication status:Published
Publication version:Version of Record
Year:2023
Number of pages:14 str.
Numbering:Vol. 15, iss. 3, art. 573
PID:20.500.12556/RUL-154097 This link opens in a new window
UDC:616-006
ISSN on article:2072-6694
DOI:10.3390/cancers15030573 This link opens in a new window
COBISS.SI-ID:138228995 This link opens in a new window
Publication date in RUL:25.01.2024
Views:331
Downloads:27
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Record is a part of a journal

Title:Cancers
Shortened title:Cancers
Publisher:MDPI
ISSN:2072-6694
COBISS.SI-ID:517914137 This link opens in a new window

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

Language:Slovenian
Keywords:glioblastom, vimentin, nanotelo

Projects

Funder:ARRS - Slovenian Research Agency
Funding programme:Young researchers

Funder:ARRS - Slovenian Research Agency
Project number:Z3-2649
Name:Določitev novih biomarkerjev glioblastoma za namen neinvazivne tekočinske biopsije

Funder:ARRS - Slovenian Research Agency
Project number:Z3-4510
Name:Vpliv imunoterapije z anti-PD-L1 atezolizumabom in nanotelesom Nb202 na organoide glioblastoma, pripravljene iz tkiva bolnikov

Funder:ARRS - Slovenian Research Agency
Project number:P1-0390
Name:Funkcijska genomika in biotehnologija za zdravje

Funder:ARRS - Slovenian Research Agency
Project number:P1-0245
Name:Ekotoksiologija, toksikološka genomika in karcinogeneza

Funder:ARRS - Slovenian Research Agency
Project number:P4-0432
Name:Morska in mikrobna biotehnologija

Funder:EC - European Commission
Funding programme:Interreg V-A It.-Slo.
Project number:146
Acronym:TRANS-GLIOMA

Funder:EC - European Commission
Funding programme:HE
Project number:101079113
Name:Twinning for excellence to strategically advance research in carcinogenesis and cancer
Acronym:CutCancer

Funder:ARRS - Slovenian Research Agency
Project number:J3-4504
Name:Z vizualizacijo mikrookolja glioblastoma do boljše terapije

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