Impact of cancer stem cell marker expression in vestibular schwannoma progression

Abstract Background: Vestibular schwannoma (VS), a benign tumor originating from the Schwann cells surrounding the 8th cranial nerve, is one of the most common intracranial tumors. Affected patients suffer from symptoms such as impaired hearing, dizziness and dysfunction of surrounding cranial nerves, which increase with the size of the VS. Although various factors influencing VS growth have been investigated, the molecular causes remain unclear. Cancer stem cells (CSC) are already known from malignant tumor entities to have the ability to self-renew and differentiate to generate and drive tumor growth. Therefore, our study investigated the influence of the expression of cancer stem cell markers in the VS progression. Methods: An exploratory study of eleven CSC markers was performed in 165 VS of different tumor volume by quantitative real-time polymerase chain reaction and correlated with preoperative tumor volume. In addition, we investigated the CSC markers Nestin, Nanog, CD44 and CD45 in selected VS primary cultures by immunofluorescence and flow cytometry. Finally, a copy number variation analysis of 26 tumor samples was performed to investigate gain or loss of CSC markers at DNA level. Results: Our results showed a strong correlation among CSC marker expression and a correlation of the tumor volume with eight CSC markers. In the VS, in particular, the expression of the markers CXCR4, CD44, CD45, Nestin, and CD133 were related to volume increase, whereas expression of SOX2, c-myc and Klf4 showed a negative correlation with the tumor volume. Using flow cytometry and immunofluorescence analysis, population of cells were detected expressing CD44 and CD45 as well as Nestin and Nanog simultaneously. Conclusion: This suggests that there is a not previously described subpopulation of CSC in VS, which is associated with an increasing tumor volume. Due to the limited treatment options available for VS, these findings could offer the possibility of targeting CSC pharmacologically to prevent tumor progression in the VS. Trial registration: The study was approved by the ethics committee of the Martin-Luther-University Halle-Wittenberg (approval number 2020-122) and ensures written informed consent of all patients.