Anti-vimentin nanobody decreases glioblastoma cell invasion in vitro and in vivo

Zottel, Alja (avtor), Novak, Metka (avtor), Šamec, Neja (avtor), Majc, Bernarda (avtor), Colja, Sara (avtor), Katrašnik, Mojca (avtor), Vittori, Miloš (avtor), Hrastar, Barbara (avtor), Rotter, Ana (avtor), Porčnik, Andrej (avtor), Lah Turnšek, Tamara (avtor), Komel, Radovan (avtor), Breznik, Barbara (avtor), Jovchevska, Ivana (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: glioblastoma, vimentin, nanobody, invasion, EMT
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta ; BF - Biotehniška fakulteta ; FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: 14 str.
• Številčenje: Vol. 15, iss. 3, art. 573
• PID: 20.500.12556/RUL-154097
• UDK: 616-006
• ISSN pri članku: 2072-6694
• DOI: 10.3390/cancers15030573
• COBISS.SI-ID: 138228995
• Datum objave v RUL: 25.01.2024

Gradivo je del revije

• Naslov: Cancers
• Skrajšan naslov: Cancers
• Založnik: MDPI
• ISSN: 2072-6694
• COBISS.SI-ID: 517914137

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: glioblastom, vimentin, nanotelo