Objective: The origin of brain tumors has attracted much controversy. Recent advances in neural stem cell biology coupled with the new concepts of central nervous system development have raised interesting possibilities regarding the oncogenic properties of neural stem/progenitor cells. To elucidate these putative properties further, the clinical materials from an infant brain tumor were analyzed, focusing on the relation with the neural stem/progenitor cells.
Methods: The expression of neural stem/progenitor cell markers in the tumor cells and the cellular components of the infant brain tumor were examined using immunohistochemistry. The tumor cell biology was analyzed both in culture and in the grafted brain environment.
Results: Three main bodies of evidence were demonstrated indicating that the tumor was of possible subventricular zone postnatal or adult normal neural stem cell origin. First, in the tumor specimen we demonstrated the strong positive expression of the neural stem/progenitor cell markers, nestin and Musashi-1. Second, immunohistochemistry revealed the presence of neuronal, astrocytic, and immature precursor cells in the tumor tissue, similar to the cellular components of the subventricular zone, thereby pointing to the subventricular zone as the possible origin of the tumor. The subventricular zone also is one of the strong candidates for the location of postnatal/adult neural stem cells. This cellular evidence was strengthened further by the clinicoradiological findings that demonstrated the involvement of the subventricular zone of the lateral ventricle by the tumor. Third, in the in vitro and in vivo experiments, a dynamic shift in expression patterns between neural stem cells (nestin, Musashi-1) and differentiated cells (glial fibrillary acidic protein, neuron-specific Class III beta-tubulin) markers was seen, similar to the proposed behavior of postnatal/adult neural stem cells in situ.
Conclusion: These findings suggest that this brain tumor originated from neural stem cells located in the subventricular zone, and the further possibility of the general oncogenic potential of neural stem cells.