CD133 suppresses neuroblastoma cell differentiation via signal pathway modification
CD133 suppresses neuroblastoma cell differentiation via signal pathway modification
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DOI：
10.1038/onc.2010.383
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发表时间：
2011-01-01
期刊：
影响因子：
8
通讯作者：
Kamijo, T.
中科院分区：
文献类型：
--
作者：
Takenobu, H.;Shimozato, O.;Kamijo, T.
CD133 （pronin -1）是一种跨膜糖蛋白，表达于正常和癌症干细胞（肿瘤起始细胞）、祖细胞、杆状光感受器细胞和多种上皮细胞表面。尽管CD133被广泛用作各种体细胞和推定的癌症干细胞的标记物，但其对癌细胞基本特性（如肿瘤发生和分化）的贡献仍有待阐明。在本报告中，我们发现CD133在几种神经母细胞瘤（NB）细胞系/肿瘤样本中表达。有趣的是，CD133抑制NB细胞的分化，如神经突的延伸和分化标记蛋白的表达，并且在几种分化刺激下被抑制，但加速NB细胞的增殖、非锚定依赖性集落形成和体内肿瘤形成。NB细胞系和原代肿瘤球实验表明，NB中cd133相关分化抑制的分子机制部分依赖于神经营养受体RET酪氨酸激酶的调控。NB细胞中的RET转录被CD133抑制，胶质细胞系来源的神经营养因子治疗不能诱导表达CD133的细胞中的RET；RET过表达挽救了cd133相关的神经突伸长抑制。值得注意的是，cd133相关的NB细胞分化和RET抑制主要依赖于p38MAPK和PI3K/Akt通路。此外，CD133在NB细胞系和原代肿瘤细胞衍生的肿瘤球中具有生长和RET表达的功能。据我们所知，这是关于CD133在癌细胞中的功能的第一篇报道，我们的发现可能用于改善NB患者的分化诱导治疗。癌症基因（2011）30,97-105；doi: 10.1038 / onc.2010.383;2010年9月6日在线发布
CD133 (prominin-1) is a transmembrane glycoprotein expressed on the surface of normal and cancer stem cells (tumor-initiating cells), progenitor cells, rod photoreceptor cells and a variety of epithelial cells. Although CD133 is widely used as a marker of various somatic and putative cancer stem cells, its contribution to the fundamental properties of cancer cells, such as tumorigenesis and differentiation, remains to be elucidated. In the present report, we found that CD133 was expressed in several neuroblastoma (NB) cell lines/tumor samples. Intriguingly, CD133 repressed NB cell differentiation, for example neurite extension and the expression of differentiation marker proteins, and was decreased by several differentiation stimuli, but accelerated cell proliferation, anchorage-independent colony formation and in vivo tumor formation of NB cells. NB cell line and primary tumor-sphere experiments indicated that the molecular mechanism of CD133-related differentiation suppression in NB was in part dependent on neurotrophic receptor RET tyrosine kinase regulation. RET transcription was suppressed by CD133 in NB cells and glial cell line-derived neurotrophic factor treatment failed to induce RET in CD133-expressing cells; RET overexpression rescued CD133-related inhibition of neurite elongation. Of note, CD133-related NB cell differentiation and RET repression were mainly dependent on p38MAPK and PI3K/Akt pathways. Furthermore, CD133 has a function in growth and RET expression in NB cell line- and primary tumor cell-derived tumor spheres. To the best of our knowledge, this is the first report of the function of CD133 in cancer cells and our findings may be applied to improve differentiation induction therapy for NB patients. Oncogene (2011) 30, 97-105; doi: 10.1038/onc.2010.383; published online 6 September 2010