Implication of tumor stem-like cells in the tumorigenesis of sporadic paraganglioma.

It is commonly believed that paragangliomas are rare tumors arising from the neural crest-derived chromaffin cells. Although it has been speculated that paraganglioma is related to stem cell origin, there has been lack of direct evidence demonstrating the presence of (neural) stem cells in these tumor tissues. In this study, we found a subgroup of human paraganglioma from ten clinical samples displayed definitive markers of CD133 and/or nestin, the fundamental features of neural stem cell capable of self-renewal and differentiation. A panel of lineage-specific markers was also manifest in some of these tumors, consistent with the hierarchical and heterogeneous nature of these tumors. These observations strongly suggest that at least some forms of paraganglioma maintain tumor stem-like cells (TSCs) that potentially contribute to the histologic complexity of human paraganglioma. Finally, we found that the genomic DNA structure becomes highly unstable in tumor cells of paraganglioma, indicating the loss of tight control of genomic surveillance system be an important transitory event from normal multi-potent tissue stem cells to TSCs.