一个软矩阵微环境通过氧化酸化依赖细胞粘附促进瘤横向扩散
Jiamin Zhong1, Jingyi Lu1, Haopeng Li1
1Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|March 15, 2026
概括
横向扩散的瘤 (LSTs) 显示出比突出的腺瘤更恶性的分子特征. 一个柔软的矩阵环境,增强的氧化酸化 (OXPHOS) 和通过ENTPD1-ADORA2B改变的粘附可能会推动LST的生长.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 横向扩散的瘤 (LSTs) 是平坦的,早期的结直肠病变经常被内镜遗漏.
- 由于与突出的腺瘤 (PA) 相比,LSTs具有独特的横向生长模式,因此具有独特的临床挑战.
- 推动LST生长的潜在分子差异仍然不太清楚.
研究的目的:
- 综合描述LST,PA和正常组织 (NT) 的分子特征,细胞表型和瘤微环境.
- 研究细胞外基质和特定分子途径在LST发育中的作用.
主要方法:
- 在临床样本上单细胞RNA测序和空间转录组学.
- 使用患者衍生器官模型.
- 对LST,PA和NT进行比较分析.
主要成果:
- LSTs表现出一种更恶性的表型,具有更高的副本数变异 (CNV) 评分和与结直肠癌更强的相关性.
- 在LST中粘附分子的下调与细胞骨变化和增强的氧化酸化 (OXPHOS) 有关.
- 在更软的细胞外基质中发现了LSTs,它促进了OXPHOS,并通过ENTPD1-ADORA2B轴调节了粘附.
结论:
- 提出了一个机械化学模型,其中软矩阵,OXPHOS和通过ENTPD1-ADORA2B的细胞骨重塑有助于LST横向生长和抑制粘附.
- 这些发现为LST发展提供了洞察力,并将ENTPD1-ADORA2B轴确定为潜在的治疗点.
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