PTX3是一种外部瘤抑制剂,可以调节癌症中补体依赖性炎症
Eduardo Bonavita1, Stefania Gentile1, Marcello Rubino1
1Humanitas Clinical and Research Center, Rozzano (Milan) 20089, Italy.
Cell
|February 14, 2015
概括
潘特拉辛3 (PTX3) 是一种关键的先天性免疫蛋白,通过调节炎症和补体激活而起瘤抑制作用. 它的缺乏通过促进瘤生长和巨细胞招募来增加癌症易感性.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 原素3 (PTX3) 对于天生的免疫和炎症调节至关重要.
- PTX3与补充因子C1q和H因子相互作用,调节补充级联.
- PTX3 缺乏与增加对致癌的易感性有关.
研究的目的:
- 研究PTX3在癌症发育和调控中的作用.
- 阐明PTX3缺乏促进瘤生长的机制.
- 探索PTX3在人类瘤中的表观遗传调节.
主要方法:
- 利用基因向的Ptx3(-/-) 小鼠研究致癌性.
- 分析了巨细胞的透,细胞因子的产生和Ptx3(-/-) 小鼠的血管生成.
- 在人类瘤中研究PTX3的表观遗传调节 (促剂甲基化).
主要成果:
- Ptx3(-/-) 小鼠表现出对致癌的敏感性增加,炎症和Trp53突变增加.
- PTX3 缺乏扩大了补充激活,CCL2 生产,并招募促进瘤的巨细胞.
- 通过促进物甲基化对PTX3的表观遗传沉默在人体瘤中观察到,例如leiomyosarcomas和结直肠癌.
结论:
- 在小鼠和人类中,PTX3作为外部瘤抑制基因起作用.
- PTX3调节补充依赖的,巨细胞介导的炎症,促进瘤的发展.
- 准PTX3或其调节通路可能为癌症提供治疗策略.
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