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在胰腺癌中维持中细胞命运需要SPP1

Huafu Li¹, Linxiang Lan^1,2, Hengxing Chen²

¹The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.

|September 24, 2025

概括

骨质素 (SPP1) 通过促进介质细胞命运来驱动胰腺癌的进展. 抑制SPP1将癌细胞转化为上皮细胞,延缓瘤的生长和转移.

科学领域:

癌症学
细胞生物学
癌症研究

背景情况:

胰腺管腺癌 (PDAC) 的进展涉及复杂的瘤细胞传播.
由GREM1对抗的骨形态蛋白 (BMP) 信号传递对于维持上皮细胞PDAC命运至关重要.
介质细胞PDAC细胞分泌GREM1,抑制BMP活动并维持上皮细胞的身份.

研究的目的:

确定胰腺癌中介质细胞命运的关键调节者.
阐明PDAC细胞命运决定的分子机制.
在PDAC中探索SPP1作为潜在的治疗点.

主要方法:

对患者血进行蛋白质组分析.
在小鼠PDAC模型中Spp1的非激活.
细胞表型转换的分析 (介质细胞转化为上皮细胞).
对受体-连接体相互作用 (SPP1-CD61) 和基因表达 (Bmp2,Grem1) 的研究.

主要成果:

在晚期PDAC中SPP1被上调,并驱动瘤形成和转移.
在小鼠中Spp1的失活会延缓瘤的生长,并防止转移.
SPP1通过CD61诱导介质PDAC细胞中的Bmp2和Grem1的表达.
通过GREM1介导的BMP抑制对于SPP1表达在上皮细胞中至关重要,形成一个调节循环.
导致SPP1功能丧失,导致细胞命运转化为介质细胞.

结论:

在PDAC中,SPP1是介质细胞命运的关键调节者.
在SPP1和GREM1之间有一个相互的环,控制PDAC细胞的可塑性.
向SPP1可能是扭转PDAC进展和转移的治疗策略.

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