在肌纤维细胞分化和功能方面,ADAMTS2和ADAMTS14的作用相反
Edward P Carter1,2,3, Kubra K Yoneten1, Nuria Gavara4
1Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.
The Journal of pathology
|November 6, 2023
概括
胰腺癌的进展涉及癌症和星状细胞之间的交叉声. 两个酶ADAMTS2和ADAMTS14通过控制转化生长因子β的可用性来调节这个过程.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 胰腺恒星细胞 (PSC) 分化为与癌症相关的肌纤维细胞,推动胰腺管腺癌 (PDAC) 的进展.
- 瘤微环境的相互作用,特别是癌细胞和PSC之间的相互作用,对于PDAC的发展至关重要.
研究的目的:
- 在3D环境中研究癌症和星状细胞之间的合作机制.
- 为了确定参与癌症星状细胞交叉和肌纤维细胞分化中的特定分子参与者.
主要方法:
- 使用人类和小鼠的癌症和星状细胞生成仿真球体.
- 大量RNA测序数据的特定物种解卷,以分析细胞类型特定的转录组.
- 功能和蛋白质组分析以阐明酶机制.
主要成果:
- 确定了体细胞特定表达的原加工酶ADAMTS2和ADAMTS14.
- 丢失ADAMTS2减少了肌纤维细胞的分化和侵入,而丢失ADAMTS14则促进了它们.
- ADAMTS2和ADAMTS14在通过不同的基质 (分别是Serpin E2和纤维素2) 调节转化生长因子β的可用性方面表现出相反的作用.
结论:
- ADAMTS2和ADAMTS14发挥了新的作用,在调节胰腺癌流体和肌纤维细胞分化方面发挥了对立的作用.
- 这些酶代表了一个新的调节轴,影响PDAC恶性行为.
- 了解这些相互作用为针对瘤微环境的治疗策略提供了洞察力.
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