TRIM28 Selective Nanobody Reduces Glioblastoma Stem Cell Invasion.

Area of Science:

• Neuro-oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Glioblastoma (GB) is an aggressive brain tumor with poor prognosis due to heterogeneity, invasion, and therapy-resistant cancer stem cells (GSCs).
• Identifying biomarkers for aggressive tumor cells and developing targeted therapies are critical for improving patient outcomes.
• Transcription factor TRIM28 has emerged as a potential biomarker in glioblastoma.

Purpose of the Study:

• To investigate the expression and role of TRIM28 in glioblastoma.
• To evaluate the therapeutic potential of targeting TRIM28 using a novel nanobody (NB237).

Main Methods:

• Quantitative analysis of TRIM28 expression in glioblastoma and low-grade glioma tissues.
• Assessment of TRIM28 expression in glioblastoma stem cells (GSCs) versus differentiated GB cells.
• In vitro and in vivo (zebrafish model) evaluation of the anti-TRIM28 nanobody NB237's efficacy in inhibiting GB cell and GSC invasiveness.
• Correlation analysis between TRIM28 expression, stem cell gene expression, and patient overall survival.

Main Results:

• TRIM28 was highly expressed in glioblastoma and low-grade gliomas, with higher, though not statistically significant, expression in GSCs compared to differentiated GB cells.
• The anti-TRIM28 nanobody NB237 significantly inhibited the invasiveness and spread of GB cells and GSCs in vitro and in vivo.
• TRIM28 was enriched in the tumor core and associated with stem cell gene expression, but did not serve as a prognostic marker for overall survival.

Conclusions:

• TRIM28 is a relevant molecular target in glioblastoma.
• The anti-TRIM28 nanobody NB237 demonstrates significant anti-invasive activity against glioblastoma cells and GSCs.
• NB237 represents a promising novel therapeutic candidate for glioblastoma treatment.