Establishment of neuroblastoma regression model and molecular mechanisms

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The Schwannian stroma in neuroblastomas is related to the prognosis of patients with neuroblastoma. There is debate surrounding the origin of Schwannian stroma in neuroblastomas : one theory being that the Schwann cells are derived from neoplastic cells, and the other that they arise from normal cells surrounding the neuroblastoma. We examined whether human bone marrow stromal cells (hBMSC) or human mesenchymal stem cells (hMSCs) differentiated into Schwann cells in neuroblastomas. HBMSCs or hMSCs with enhanced green fluorescent protein (EGFP) were injected into xenotransplanted neuroblastomas in non-obese diabetic mice with severe combined immunodeficiency and the resulting tumor analyzed using immunohistochemistry. HBMSCs or hMSCs were also co-cultured with neuroblastoma cells, and the induction of Schwann cell-specific molecules, S100beta and Egr-2, was monitored. S100beta-positive Schwannian stroma was only observed in the neuroblastomas containing hBMSCs or hMSCs, and not in the neuroblastomas without hBMSCs or hMSCs. Double-staining with anti-S100 and anti-EGFP showed that S100-positive cells in neuroblastomas were also EGFP-positive. By contrast, hBMSCs didn't develop into Schwann cells in Ewing's sarcoma. These results showed the transplanted hBMSCs or hMSCs differentiated into Schwann cells specifically in neuroblastomas. S100beta and Egr-2 were expressed in hBMSCs or hMSCs co-cultured with neuroblastoma cells. HBMSCs or hMSCs may contribute to the formation of human tumor stroma and the Schwannian stroma of neuroblastomas may be derived from non-neoplastic stromal cells.