通过不同的激活途径诱导的血小板衍生的细胞外囊通过功能和转录性变化驱动黑色素瘤的进展
Zeynep Tavukcuoglu1, Umar Butt1, Alessandra V S Faria1,2
1EV group, Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, and CURED, Drug Research Program, Faculty of Pharmacy, Division of Pharmaceutical Biosciences, University of Helsinki, Viikinkaari 9, Helsinki, 00790, Finland.
Cell communication and signaling : CCS
|December 19, 2024
概括
血小板衍生的细胞外囊泡 (PEVs) 可以通过改变癌细胞功能来促进黑色素瘤转移. 不同类型的PEV通过特定的血小板激活产生,对癌症特征表现出不同的影响,提供潜在的治疗点.
科学领域:
- 在瘤学瘤学.
- 血液学 血液学 血液学
- 细胞生物学 细胞生物学
背景情况:
- 血小板除了血液静止之外,还通过与癌细胞的相互作用促进癌症转移.
- 血小板衍生的细胞外囊泡 (PEVs) 可以影响瘤微环境和循环中的癌细胞形成.
- 不同的血小板激活途径产生不同的PEV类型,对癌症进展产生不同的影响.
研究的目的:
- 研究各种PEV类型对黑色素瘤特征功能的差异影响,包括扩散,入侵和血管生成.
- 分析PEV治疗后癌细胞转录组和细胞外囊 (EV) 档案的变化.
- 确定特定的血小板激活路径,产生具有显著癌症促进性质的PEVs.
主要方法:
- 人类黑色素瘤细胞系 (MV3,A2058) 被培养成3D球形.
- 人体血小板被激活使用原相关 (CRP),fucoidan (FFV),血/原或离子体产生不同的PEVs.
- PEVs被分离并用于治疗黑色素瘤球体,随后进行功能测定和RNA测序.
主要成果:
- 由CRP和FFV产生的PEV显著增加了黑色素瘤细胞的增殖.
- 所有经过测试的PEV类型都在黑色素瘤EV中诱导了独特的四氨酸标志.
- 在CRP和FFVPEV中差异调节PI3K-Akt,MAPK,TGF-β和I型干扰素信号通路.
结论:
- PEVs表现出共同和独特的促进癌症的功能,影响黑色素瘤细胞转录组和转移潜力.
- 针对参与PEV生成的血小板受体可能为癌症治疗提供新的治疗策略.
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