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低级和高级质瘤内皮细胞差异调节瘤生长

Sree Deepthi Muthukrishnan, Haocheng Qi, David Wang

bioRxiv : the preprint server for biology

|July 18, 2023

概括

在低度质瘤 (LGG) 和高度质瘤 (HGG) 中,瘤内皮细胞 (TEC) 不同. LGG-TECs抑制IDH野生型质母细胞瘤的生长,而HGG-TECs促进它,揭示了质瘤进展中的不同作用.

科学领域:

神经瘤学神经瘤学
癌症生物学癌症生物学
分子瘤学分子瘤学

背景情况:

高度质瘤 (HGG) 与低度质瘤 (LGG) 相比,表现出显著的新血管化和内皮细胞增殖.
HGG中的瘤内皮细胞 (TEC) 与正常的大脑EC不同,分泌促进质瘤生长的因素.
在LGG中TECs的作用及其对质瘤生长的贡献仍然不太清楚.

研究的目的:

研究LGG和HGG的TEC之间的分子和功能差异.
确定LGG和HGG-TEC对质瘤生长和进展的不同贡献.
为了确定由TECs分泌的特定因素,影响质瘤细胞行为.

主要方法:

从II级/III级 (LGG,IDH-突变) 和IV级 (HGG,IDH-野生型) 质瘤中对TEC进行转录基因分析.
功能性测试评估TECs的生长,抗血管原药物耐药性和放射治疗反应.
在体外和体外研究使用条件介质和TEC的特定因子在患者衍生的质球线和正位异种移植模型上.

主要成果:

LGG-TECs显示在细胞外基因和细胞周期基因中的丰富性,以及对抗血管生成疗法的敏感性.
HGG-TECs 显示了与免疫反应相关的基因组的增加以及对抗血管生成疗法的抵抗性.
LGG-TEC和HGG-TEC对IDH野生型和突变瘤细胞的生长有不同的影响;来自LGG-TEC的阿斯波林 (ASPN) 通过调节TGF-β1-GPM6A信号,抑制了IDH野生型质母细胞瘤的生长.

结论:

来自LGG和HGG的TEC在分子和功能上是异质的.
LGG和HGG-TEC不同调节IDH野生型和突变性质瘤的生长.
TECs代表不同的治疗点,取决于质瘤等级和IDH突变状态.

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