Establishment of neuroblastoma regression model and molecular mechanisms

神经母细胞瘤中的许旺间质与神经母细胞瘤患者的预后有关。关于神经母细胞瘤中许旺细胞间质的起源存在争议：一种理论认为许旺细胞来自肿瘤细胞，另一种理论认为它们来自神经母细胞瘤周围的正常细胞。我们研究了人骨髓基质细胞（hBMSC）或人间充质干细胞（hMSCs）是否在神经母细胞瘤中分化为雪旺细胞。将HBMSCs或增强绿色荧光蛋白（EGFP）的hMSCs注射到患有严重联合免疫缺陷的非肥胖糖尿病小鼠的异种移植神经母细胞瘤中，并使用免疫组织化学分析所产生的肿瘤。HBMSCs或hMSCs也与神经母细胞瘤细胞共培养，并监测雪旺细胞特异性分子s100 β和Egr-2的诱导情况。s100 - β阳性的许旺氏间质仅在含有hBMSCs或hMSCs的神经母细胞瘤中观察到，而在不含hBMSCs或hMSCs的神经母细胞瘤中未观察到。抗s100和抗egfp双染色显示，神经母细胞瘤中s100阳性细胞也呈egfp阳性。相比之下，hBMSCs在尤文氏肉瘤中没有发育成雪旺细胞。结果表明，移植的骨髓间充质干细胞或骨髓间充质干细胞在神经母细胞瘤中特异分化为雪旺细胞。s100 β和Egr-2在hBMSCs或与神经母细胞瘤细胞共培养的hMSCs中表达。骨髓间充质干细胞或骨髓间充质干细胞可能有助于人类肿瘤间质的形成，神经母细胞瘤的许旺氏间质可能来源于非肿瘤间质细胞。

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.