BMP signaling induces astrocytic differentiation of clinically derived oligodendroglioma propagating cells.
BMP signaling induces astrocytic differentiation of clinically derived oligodendroglioma propagating cells.
复制标题
BMP 信号传导诱导临床来源的少突神经胶质瘤增殖细胞的星形胶质细胞分化。
DOI：
10.1158/1541-7786.mcr-13-0349
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kessler,JohnA
中科院分区：
文献类型：
--
作者：
Srikanth,Maya;Kim,Juno;Das,Sunit;Kessler,JohnA
少突胶质细胞瘤是一种缺乏详细研究的神经胶质细胞瘤，因为无法培养出忠实再现其突出特性的少突胶质细胞瘤细胞。我们已经成功地从多个临床少突胶质细胞瘤标本中分离和增殖胶质瘤干细胞样细胞。这些少突胶质细胞瘤增殖细胞（OligPC）是多能的，并形成具有少突胶质细胞瘤特征的异种移植物。骨形态发生蛋白（BMP）被认为是发育过程中少突胶质细胞生成的有效抑制剂;因此，对BMP信号传导在OligPC中的作用进行了表征。BMP途径组分由OligPC表达，并且经由Smad蛋白的经典信号传导是完整的。这种信号传导有效地消耗CD 133阳性OligPC，降低增殖，并诱导星形胶质细胞分化。此外，分析表明，BMP信号效应子ID 2和ID 4对少突胶质细胞分化因子OLIG 1/2的细胞质封存是一种合理的潜在机制。这些发现阐明了BMP信号传导对少突胶质细胞瘤干细胞样细胞的影响的分子途径。意义：干细胞样细胞能够增殖少突胶质细胞瘤，BMP信号传导通过诱导星形胶质细胞分化有效地减少其干细胞性，表明BMP活化可能是有效的癌症干细胞靶向治疗。Mol Cancer Res; 12（2）; 283-94。©2013 AACR。
Oligodendrogliomas are a type of glioma that lack detailed investigation because of an inability to cultivate oligodendroglioma cells that faithfully recapitulate their salient qualities. We have successfully isolated and propagated glioma stem-like cells from multiple clinical oligodendroglioma specimens. These oligodendroglioma-propagating cells (OligPC) are multipotent and form xenografts with oligodendroglioma features. Bone morphogenetic proteins (BMP) are considered potent inhibitors of oligodendrogliogenesis during development; therefore, the effects of BMP signaling in OligPCs were characterized. BMP pathway components are expressed by OligPCs and canonical signaling via Smad proteins is intact. This signaling potently depletes CD133-positive OligPCs, decreasing proliferation, and inducing astrocytic differentiation. Furthermore, analyses revealed that cytoplasmic sequestration of the oligodendrocyte differentiation factors OLIG1/2 by the BMP signaling effectors ID2 and ID4 is a plausible underlying mechanism. These findings elucidate the molecular pathways that underlie the effects of BMP signaling on oligodendroglioma stem-like cells.Implications:Stem-like cells are capable of propagating oligodendrogliomas, and BMP signaling potently diminishes their stemness by inducing astrocytic differentiation, suggesting that BMP activation may be effective as a cancer stem cell–targeted therapy.Mol Cancer Res; 12(2); 283–94. ©2013 AACR.