纤维素作为瘤细胞与血小板相互作用的媒介
Ivan Tesakov1,2, Anna D Korneichuk1,3, Aleksandra A Filkova1,3
1Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, 1 Samory Mashela Str., 117997, Moscow, Russia.
癌症转移包括瘤细胞和血小板,但抗血小板药物不足. 抗凝剂,而不是抗血小板剂,通过抑制纤维素的形成,有效地防止瘤细胞诱导的血小板聚合,从而减少转移.
科学领域:
- 在瘤学瘤学.
- 血液学 血液学 血液学
- 生物化学 生物化学
背景情况:
- 转移,一种关键的癌症并发症,涉及瘤细胞-血小板相互作用.
- 目前的抗血小板疗法在改善癌症存活率方面表现出有限的有效性.
- 了解瘤细胞-血小板相互作用的精确机制对于开发有效的抗转移策略至关重要.
研究的目的:
- 为了研究血小板聚合在癌症转移中的作用.
- 阐明瘤细胞诱导的血小板聚合 (TCIPA) 背后的机制.
- 评估抗凝血治疗与抗血小板治疗在预防转移方面的有效性.
主要方法:
- 使用光传输聚合计,流细胞计和共聚焦显微镜来描述人类血小板与瘤细胞的相互作用.
- 用一个路易斯癌的小鼠模型来评估抗血小板和抗凝固疗法的体内效应.
- 进行了体外测试,以分析,血蛋白和纤维素聚合在TCIPA中的作用.
主要成果:
- TCIPA与瘤细胞系侵入性相关,需要和血蛋白.
- 肝素,里瓦洛克萨班和达比加特兰完全消除了TCIPA,而血小板抑制只有轻微的影响.
- 瘤细胞诱导了X因子依赖性纤维素聚合,将血小板困在网格内,这是由GPRP抑制的过程.
- 抗凝血和抗血小板治疗都减少了小鼠模型中的肺转移.
结论:
- 瘤细胞诱导的血小板聚合主要由纤维素形成介导,不一定是血小板激活.
- 抗凝固疗法有效地防止了由纤维素稳定的血小板瘤细胞异质聚合物的形成.
- 向纤维素形成是一个有前途的治疗策略,可以抑制癌症转移.
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