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神经嵴衍生的祖细胞在4期/M期神经母细胞瘤中对肿瘤基质和侵袭性有影响。

Neural crest derived progenitor cells contribute to tumor stroma and aggressiveness in stage 4/M neuroblastoma.

作者信息

Linares-Clemente Pedro, Aguilar-Morante Diana, Rodríguez-Prieto Ismael, Ramírez Gema, de Torres Carmen, Santamaría Vicente, Pascual-Vaca Diego, Colmenero-Repiso Ana, Vega Francisco M, Mora Jaume, Cabello Rosa, Márquez Catalina, Rivas Eloy, Pardal Ricardo

机构信息

Instituto de Biomedicina de Sevilla (IBiS), Departamento de Fisiología Médica y Biofísica, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Sevilla, Spain.

Departamento de Oncología Pediátrica, Hospital Universitario Virgen del Rocío, Sevilla, Spain.

出版信息

Oncotarget. 2017 Sep 21;8(52):89775-89792. doi: 10.18632/oncotarget.21128. eCollection 2017 Oct 27.

DOI:10.18632/oncotarget.21128
PMID:29163787
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5685708/
Abstract

Pediatric tumors arise upon oncogenic transformation of stem/progenitor cells during embryonic development. Given this scenario, the existence of non-tumorigenic stem cells included within the aberrant tumoral niche, with a potential role in tumor biology, is an intriguing and unstudied possibility. Here, we describe the presence and function of non-tumorigenic neural crest-derived progenitor cells in aggressive neuroblastoma (NB) tumors. These cells differentiate into neural crest typical mesectodermal derivatives, giving rise to tumor stroma and promoting proliferation and tumor aggressiveness. Furthermore, an analysis of gene expression profiles in stage 4/M NB revealed a neural crest stem cell (NCSC) gene signature that was associated to stromal phenotype and high probability of relapse. Thus, this NCSC gene expression signature could be used in prognosis to improve stratification of stage 4/M NB tumors. Our results might facilitate the design of new therapies by targeting NCSCs and their contribution to tumor stroma.

摘要

小儿肿瘤起源于胚胎发育过程中干细胞/祖细胞的致癌转化。鉴于此情况，异常肿瘤微环境中存在的非致瘤性干细胞在肿瘤生物学中可能发挥作用，这是一个引人入胜但尚未研究的可能性。在这里，我们描述了侵袭性神经母细胞瘤（NB）肿瘤中神经嵴来源的非致瘤性祖细胞的存在和功能。这些细胞分化为神经嵴典型的中胚层衍生物，形成肿瘤基质并促进增殖和肿瘤侵袭性。此外，对4期/M期NB的基因表达谱分析揭示了一种神经嵴干细胞（NCSC）基因特征，该特征与基质表型和高复发概率相关。因此，这种NCSC基因表达特征可用于预后，以改善4期/M期NB肿瘤的分层。我们的结果可能有助于通过靶向NCSCs及其对肿瘤基质的贡献来设计新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/883714f223d0/oncotarget-08-89775-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/43d3c2d7c0bd/oncotarget-08-89775-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/15920c500c97/oncotarget-08-89775-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/df944e217401/oncotarget-08-89775-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/944574d473ef/oncotarget-08-89775-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/98c5bb9ab632/oncotarget-08-89775-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/883714f223d0/oncotarget-08-89775-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/43d3c2d7c0bd/oncotarget-08-89775-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/15920c500c97/oncotarget-08-89775-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/df944e217401/oncotarget-08-89775-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/944574d473ef/oncotarget-08-89775-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/98c5bb9ab632/oncotarget-08-89775-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c6/5685708/883714f223d0/oncotarget-08-89775-g006.jpg

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Gene Expression Profiling Supports the Neural Crest Origin of Adult Rodent Carotid Body Stem Cells and Identifies CD10 as a Marker for Mesectoderm-Committed Progenitors.基因表达谱分析支持成年啮齿动物颈动脉体干细胞的神经嵴起源，并将CD10鉴定为中胚层定向祖细胞的标志物。
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Concise Review: Paracrine Role of Stem Cells in Pituitary Tumors: A Focus on Adamantinomatous Craniopharyngioma.
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