瘤血管化通过质母细胞类干细胞的内皮分化
Lucia Ricci-Vitiani1, Roberto Pallini, Mauro Biffoni
1Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.
Nature
|November 25, 2010
概括
质母细胞类干细胞可以产生功能性内皮细胞,形成瘤血管. 这一发现揭示了瘤血管形成的新机制,并表明质母细胞瘤血管系统的很大一部分具有瘤起源.
科学领域:
- 在瘤学瘤学.
- 干细胞生物学 干细胞生物学
- 血管生物学 血管生物学
背景情况:
- 质母细胞瘤是一种高度血管性脑瘤.
- 质母细胞类干细胞 (GSCs) 维持瘤,并且可能具有更广泛的分化潜力.
- 神经干细胞可以分化为内皮细胞,这表明神经和血管区之间存在联系.
研究的目的:
- 为了调查质母细胞内内皮质细胞的起源.
- 为了确定质母细胞类干细胞是否能产生功能性内皮细胞.
- 为了探索瘤血管生成的新机制.
主要方法:
- 在质母细胞瘤样本中的内皮细胞的基因组分析.
- 在内皮细胞培养条件下GSCs的体外分化.
- 在免疫功能低下的小鼠中进行GSC外移植,以评估瘤血管化.
- 在老鼠异种移植中针对GSC衍生的内皮细胞的向治疗.
主要成果:
- 显著的百分比 (平均60.7%) 的质母细胞内皮细胞与瘤细胞具有相同的基因组变异,表明其瘤起源.
- 在内皮条件下培养的GSC分化为具有内皮表型和功能的细胞.
- 在小鼠中进行的GSC异体移植显示出主要由GSC衍生的人体内皮细胞组成的血管化.
- 准GSC衍生的内皮细胞导致异种移植中的瘤减少和退化.
结论:
- 质母细胞类干细胞可以分化为功能性内皮细胞,有助于瘤血管.
- 这一发现为瘤血管生成提供了一个新的机制,并表明癌症干细胞可以形成瘤血管.
- 这项研究强调了瘤内皮的很大一部分的潜在瘤起源及其在质母细胞瘤进展中的功能相关性.
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