Activation of PDGFR and EGFR promotes the acquisition of a stem cell-like phenotype in schwannomas.

OBJECTIVES

Vestibular schwannomas (VS) are benign tumors that arise from unregulated growth of Schwann cells. Both benign and malignant tumors are believed to contain tumor stem cells that are hypothesized to originate from dysregulation of tumor suppressors and oncogenes. We aimed to determine if schwannoma cells express stem cell genes and markers and if activation of the proto-oncogenes epidermal growth factor receptor and platelet-derived growth factor receptor would regulate the stem cell properties of these cells.

METHODS

Immunohistochemical staining was used to determine the expression of stem cell genes in archived VS tissue, immunofluorescence was used to investigate the expression in cell lines, and Western blot analysis was used to measure PDGFR expression in vestibular schwannoma tissue. Upon activation of PDGFR or EGFR in schwannoma cell lines using specific ligands, flow cytometry was used to quantify the side population (SP), stem cell genes were measured using quantitative PCR, and tumorsphere-forming ability was determined.

RESULTS

Stem cell genes are expressed in vestibular schwannoma tissue and schwannoma cell lines. Activation of both EGFR and PDGFR resulted in increase in the induction of the expression of the stem cell genes Oct-4 and Nanog and marked increase in tumorsphere-forming ability, but only PDGFR activation resulted in an increase in the side population in JS1 cells.

CONCLUSION

Dysregulation of EGFR and PDGFR promotes the acquisition of a stem cell-like phenotype in schwannnoma cells that may be critical in vestibular schwannoma tumorigenesis.