德斯莫索姆突变影响瘤微环境,促进黑色素瘤的扩散
Maayan Baron1,2, Mohita Tagore3,2, Patrick Wall1
1Department of Medicine, University of California San Diego, La Jolla, CA USA.
bioRxiv : the preprint server for biology
|October 3, 2023
概括
人类癌症中,特别是黑色素瘤中,基因变异常见. 邻近细胞的突变可以减少德斯莫索姆基因表达,促进黑色素瘤细胞的增殖.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 分子生物学分子生物学
背景情况:
- 德斯莫索姆对于上皮组织中细胞对细胞的粘附至关重要.
- 人类癌症中经常观察到德斯莫索姆的遗传变化.
- 皮肤黑色素瘤表现出高突变率的desmosome基因 (>70%的病例).
研究的目的:
- 为了研究在人类癌症,特别是黑色素瘤中德斯莫索姆基因变化的作用.
- 了解德斯莫索姆突变对德斯莫索姆基因表达和黑色素瘤细胞行为的影响.
- 探索潜在的微环境对黑色素瘤发展的贡献.
主要方法:
- 在各种人类癌症中对desmosome基因的遗传改变的分析.
- 在黑色素瘤活检中的基因表达水平与desmosome基因突变的相关性.
- 空间转录学和蛋白质免疫光学以定位基因表达变化.
- 在体外共同培养实验中,使用了角质细胞和黑色素瘤细胞.
- 评估黑色素瘤细胞的扩散,以应对脱素缺乏的角质细胞.
主要成果:
- 在人类癌症中发现了经常发生的基因变异,皮肤黑色素瘤的患病率很高.
- 在一次性黑色素瘤中,desmosome基因的更高突变负担与减少的desmosome基因表达相关.
- 空间分析表明,瘤微环境的角质细胞,而不是黑色素瘤细胞中发生了减少的desmosome基因表达.
- 在角质细胞中,desmosome基因被淘汰导致相邻黑色素瘤细胞的增多.
- 由脱素缺乏的角质细胞条件下的介质也增强了黑色素瘤细胞的增殖.
结论:
- 瘤微环境中的德斯莫索姆突变,特别是质细胞中的德斯莫索姆突变,可以减少德斯莫索姆基因表达.
- 在微环境中,这种降低了desmosome基因表达,促进了黑色素瘤细胞的增殖.
- 在邻近细胞中累积的脱细胞突变可能会导致黑色素瘤的发展和进展.
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