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白色脂肪组织中的内皮Notch1信号促进癌症缓解症
Jacqueline Taylor1, Leonie Uhl1,2, Iris Moll1
1Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Nature cancer
|September 25, 2023
概括
癌症缓解症涉及组织浪费. 这项研究揭示了瘤在白脂肪组织 (WAT) 内皮中激活了Notch1信号,导致视网膜酸的产生和WAT的浪费,提供了一个新的治疗点.
科学领域:
- 在瘤学瘤学.
- 血管生物学 血管生物学
- 代谢疾病 代谢疾病
背景情况:
- 癌症缓解症是癌症发病率和死亡率的一个关键因素,其特点是显著的体重减轻.
- 白色脂肪组织 (WAT) 的重塑,包括受损的脂质储存,炎症和纤维化,先于和有助于缓冲症.
- 众所周知,瘤分泌的因素会诱导组织消耗,但内皮在协调这一过程中的作用尚不清楚.
研究的目的:
- 为了研究白色脂肪组织 (WAT) 内皮在调解癌症缓解症中的作用.
- 为了确定内皮信号是否在癌症进展过程中协调WAT重塑和组织损耗.
主要方法:
- 利用人类和小鼠的癌症模型来研究前.
- 在WAT内皮中分析了Notch1信号激活.
- 研究了网膜酸生产在WAT浪费中的作用.
- 评估了对视网膜酸信号的药理阻断的疗效.
主要成果:
- 发现瘤在预卡切西亚期间过度激活了WAT内皮中的Notch1信号.
- 在雄性小鼠中,持续的内皮细胞Notch1信号导致了过度的视网膜酸生产和WAT浪费.
- 阻断视网氨酸信号传递有效地抑制了小鼠癌症缓解症模型中的WAT浪费.
结论:
- 内皮在编排癌症缓解症期间的WAT重塑和浪费方面发挥着至关重要的作用.
- 癌症通过Notch1信号来操纵遥远的WAT内皮,通过改变的血管新生信号,特别是视网酸,诱导消耗.
- 准视网膜酸信号传输是对抗癌症食症的潜在治疗策略.
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