DLL4/Notch3/WNT5B轴介导黑色素瘤和淋巴内皮细胞之间的双向前列腺瘤交叉
Sanni Alve1, Silvia Gramolelli2,3, Joonas Jukonen1
1Translational Cancer Medicine Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
JCI insight
|November 16, 2023
概括
黑色素瘤细胞与淋巴血管相互作用,上调WNT5B. 这种分子通过改变淋巴内皮细胞功能,促进瘤细胞逃到淋巴结,促进黑色素瘤转移.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 黑色素瘤的进展与淋巴血管的相互作用有关.
- 驱动这种黑色素瘤-淋巴结交的分子机制尚未完全理解.
研究的目的:
- 研究调解黑色素瘤细胞和淋巴内皮细胞 (LEC) 之间的双向交叉声的分子因素.
- 阐明特定信号通路在通过淋巴相互作用促进黑色素瘤转移中的作用.
主要方法:
- 人类初级LEC与人类黑色素瘤细胞系的共同培养.
- 对LEC进行转录基因分析.
- 在WNT5B的消耗实验中.
- 在患者样本中分析Notch3和WNT5B表达.
主要成果:
- 黑色素瘤-LEC共同培养诱导了LECs的转录和功能变化.
- 黑色素瘤细胞上调的WNT5B调节LEC功能变化并促进黑色素瘤细胞转移.
- 黑色素瘤细胞中的Notch3/WNT5B轴是由来自LEC的DLL4诱导的.
- 由于WNT5B的枯竭,导致黑色素瘤细胞逃到淋巴结的功能受损.
结论:
- WNT5B是黑色素瘤-淋巴细胞内皮细胞交叉的关键分子媒介.
- 鉴定到的Notch3/WNT5B信号轴促进了黑色素瘤细胞的转移潜力.
- 向WNT5B可能是抑制黑色素瘤转移的治疗策略.
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