TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion

Molecules

Miloš Vittori¹  Barbara Hrastar²  Ana Rotter²  Metka Novak²  Barbara Breznik²  Bernarda Majc²  Tamara Lah Turnšek²  Andrej Porčnik³  Neja Šamec⁴  Ivana Jovčevska⁴  Radovan Komel⁴  Alja Zottel⁴ 

[1] Department of Biology, Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia;Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia;Department of Neurosurgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia;Medical Centre for Molecular Biology, Institute for Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia;

关键词: glioblastoma;    nanobody;    glioblastoma stem cells;    cell invasion;    transcription factor;    TRIM28;   

DOI  :  10.3390/molecules26175141

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown