纤维素构成和转胺酶2交联合作调节卵巢癌细胞粘附在ECM模拟结构
Ning Yang1, Ali Abbaspour2, James M Considine3
1Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
Acta biomaterialia
|September 20, 2025
概括
卵巢癌中的瘤进展是由细胞外基质 (ECM) 的变化所支持的. 我们发现,质胺酶2 (TG2) 对原蛋白和纤维蛋白的交联增加了高度的卵巢癌细胞粘附.
科学领域:
- 生物材料科学 生物材料科学
- 癌症生物学 癌症生物学
- 细胞外矩阵研究研究
背景情况:
- 细胞外基质 (ECM) 对瘤进展至关重要,特别是在高度血清性卵巢癌 (HGSOC) 中.
- 在HGSOC中,口腔转移显示了高水平的原I和细胞纤维素 (cFN),并增加了原I纤维厚度.
- 转胺酶2 (TG2) 是一种ECM交叉链接酶,在omental转移的细胞外环境中被上调并活跃.
研究的目的:
- 研究ECM变化的影响,特别是原I,cFN和TG2活性对HGSOC细胞粘附的影响.
- 使用TG2开发新的ECM结构,以回顾关键的转移性ECM特征.
- 探索连接体身份和纤维直径在工程ECM内调解HGSOC细胞粘附中的作用.
主要方法:
- 从HGSOC患者的正常和转移性体质中分析原I和cFN水平和纤维厚度.
- 开发ECM水凝结构,使用原I,cFN和血纤维蛋白 (pFN).
- 利用TG2作为交联剂来修改ECM结构,并使用不同的凝成分和纤维厚度评估HGSOC细胞粘附.
主要成果:
- 在仅使用I型原体凝时,HGSOC细胞粘附率较低,但在添加cFN或pFN时增加.
- 通过TG2介导的原I/cFN水凝的交叉链接显著促进了HGSOC细胞粘附,而原I/pFN交叉链接没有影响.
- 当纤维厚度不变时,HGSOC细胞粘附取决于纤维厚度和连接体身份;当纤维厚度不变时,cFN的含有会比pFN或原I增强粘附. 增加纤维厚度也促进了粘附.
结论:
- 改变OMM转移的ECM组成和结构,包括增加原I纤维厚度和TG2活性,可以支持HGSOC的进展.
- 像cFN这样的特定ECM组件的TG2介导的交叉链接可以增强瘤细胞粘附.
- 这些发现为ECM在指导细胞行为的作用提供了洞察力,并为开发调节细胞粘附的材料提供了一种新的仿生方法.
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