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The Bi-(AID-1-T) G-Quadruplex Has a Janus Effect on Primary and Recurrent Gliomas: Anti-Proliferation and
Svetlana Pavlova1, Lika Fab1, Ekaterina Savchenko2
1Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia.
Abstract:
High-grade gliomas are considered an incurable disease. Despite all the various therapy options available, patient survival remains low, and the tumor usually returns. Tumor resistance to conventional therapy and stimulation of the migratory activity of surviving cells are the main factors that lead to recurrent tumors. When developing new treatment approaches, the effect is most often evaluated on standard and phenotypically depleted cancer cell lines. Moreover, there is much focus on the anti-proliferative effect of such therapies without considering the possible stimulation of migratory activity. In this paper, we studied how glioma cell migration changes after exposure to bi-(AID-1-T), an anti-proliferative aptamer. We investigated the effect of this aptamer on eight human glioma cell cultures (Grades III and IV) that were derived from patients' tumor tissue; the difference between primary and recurrent tumors was taken into account. Despite its strong anti-proliferative activity, bi-(AID-1-T) was shown to induce migration of recurrent tumor cells. This result shows the importance of studying the effect of therapeutic molecules on the invasive properties of glioma tumor cells in order to reduce the likelihood of inducing tumor recurrence.
Insights
High-grade gliomas are incurable, often recurring after treatment. This study found that the anti-proliferative aptamer bi-(AID-1-T) can unexpectedly increase glioma cell migration, highlighting the need to assess invasiveness in new therapies.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Molecular Therapy
Background:
- High-grade gliomas (HGGs) remain incurable, with low patient survival rates and frequent recurrence.
- Tumor resistance and enhanced cell migration are key factors driving HGG recurrence.
- Current therapeutic development often overlooks the impact on cell migration, focusing solely on anti-proliferative effects.
Purpose of the Study:
- To investigate the effect of the anti-proliferative aptamer bi-(AID-1-T) on glioma cell migration.
- To evaluate the impact of bi-(AID-1-T) on primary and recurrent human glioma cell cultures.
- To assess the potential of therapeutic agents to induce invasive properties in HGG cells.
Main Methods:
- Culturing eight distinct human glioma cell lines (Grades III and IV) derived from patient tumor tissue.
- Exposing glioma cells to the anti-proliferative aptamer bi-(AID-1-T).
- Analyzing changes in glioma cell migration patterns post-treatment.
Main Results:
- The aptamer bi-(AID-1-T) demonstrated significant anti-proliferative activity.
- Bi-(AID-1-T) exposure induced increased migration in recurrent glioma cells.
- Differential effects on cell migration were observed between primary and recurrent tumor cells.
Conclusions:
- Therapeutic molecules targeting gliomas must be evaluated for their impact on cell invasiveness.
- The anti-proliferative aptamer bi-(AID-1-T) may inadvertently promote HGG recurrence by stimulating cell migration.
- Considering both anti-proliferative and pro-migratory effects is crucial for developing effective HGG treatments.
