Adult human neural progenitor and stem cells have been implicated as a potential source of brain cancer causing cells, but specific events that might cause cells to progress towards a transformed phenotype remain unclear. The L1CAM (L1) cell adhesion/recognition molecule is expressed abnormally by human glioma cancer cells and is released as a large extracellular ectodomain fragment, which stimulates cell motility and proliferation. This study investigates the effects of ectopic overexpression of the L1 long ectodomain (L1LE; ˜180 kDa) on the motility, proliferation, and differentiation of human neural progenitor cells (HNPs). L1LE was ectopically expressed in HNPs using a lentiviral vector. Surprisingly, overexpression of L1LE resulted in reduced HNP motility in vitro, in stark contrast to the effects on glioma and other cancer cell types. L1LE overexpression resulted in a variable degree of maintenance of HNP proliferation in media without added growth factors but did not increase proliferation. In monolayer culture, HNPs expressed a variety of differentiation markers. L1LE overexpression resulted in loss of glutamine synthetase (GS) and β3‐tubulin expression in normal HNP media, and reduced vimentin and increased GS expression in the absence of added growth factors. When co‐cultured with chick embryonic brain cell aggregates, HNPs show increased differentiation potential. Some HNPs expressed p‐neurofilaments and oligodendrocytic O4, indicating differentiation beyond that in monolayer culture. Most HNP‐L1LE cells lost their vimentin and GFAP (glial fibrillary acidic protein) staining, and many cells were positive for astrocytic GS. However, these cells rarely were positive for neuronal markers β3‐tubulin or p‐neurofilaments, and few HNP oligodendrocyte progenitors were found. These results suggest that unlike for glioma cells, L1LE does not increase HNP cell motility, but rather decreases motility and influences the differentiation of normal brain progenitor cells. Therefore, the effect of L1LE on increasing motility and proliferation appears to be limited to already transformed cells.

中文翻译：

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L1CAM 胞外域的异位表达改变分化和运动，但不改变人类神经祖细胞的增殖

成人神经祖细胞和干细胞被认为是导致脑癌的细胞的潜在来源，但可能导致细胞向转化表型发展的特定事件仍不清楚。L1CAM (L1) 细胞粘附/识别分子由人神经胶质瘤癌细胞异常表达，并作为大的细胞外胞外域片段释放，刺激细胞运动和增殖。该研究调查了 L1 长胞外域 (L1LE；～180 kDa) 的异位过表达对人类神经祖细胞 (HNP) 的运动性、增殖和分化的影响。L1LE 使用慢病毒载体在 HNP 中异位表达。令人惊讶的是，L1LE 的过表达导致体外 HNP 运动性降低，这与对神经胶质瘤和其他癌细胞类型的影响形成鲜明对比。L1LE 过表达导致培养基中 HNP 增殖的不同程度维持，但没有添加生长因子，但不会增加增殖。在单层培养中，HNPs 表达了多种分化标志物。L1LE 过表达导致正常 HNP 培养基中谷氨酰胺合成酶 (GS) 和 β3-微管蛋白表达的丧失，并在没有添加生长因子的情况下降低波形蛋白和增加 GS 表达。当与鸡胚胎脑细胞聚集体共培养时，HNPs 显示出更高的分化潜能。一些 HNPs 表达 p 神经丝和少突胶质细胞 O4，表明分化超出了单层培养。大多数 HNP-L1LE 细胞失去波形蛋白和 GFAP（胶质纤维酸性蛋白）染色，许多细胞呈星形胶质细胞 GS 阳性。然而，这些细胞很少对神经元标记物 β3-微管蛋白或 p-神经丝呈阳性，并且很少发现 HNP 少突胶质祖细胞。这些结果表明，与胶质瘤细胞不同，L1LE 不会增加 HNP 细胞的运动性，而是降低运动性并影响正常脑祖细胞的分化。因此，L1LE 对增加运动和增殖的影响似乎仅限于已经转化的细胞。