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回收黑色素瘤分泌的黑色素体调节与瘤相关的巨细胞多样化

Roma Parikh¹, Shivang Parikh^1,2, Daniella Berzin³

¹Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.

The EMBO journal

|May 8, 2024

概括

黑色素体是一种细胞外囊泡 (EV),可以在细胞之间转移,影响巨细胞的行为并促进黑色素瘤转移. 阻止这些"二手"EV信号可能会阻止癌症的进展.

科学领域:

细胞生物学细胞生物学
癌症研究癌症研究
免疫学免疫学免疫学

背景情况:

细胞外囊泡 (EVs) 中介细胞间通信.
黑色素体是黑色素细胞分泌的大型EVs,用于黑色素的运输.
小EV通常会在受体细胞内分解.

研究的目的:

研究一种涉及黑色素体的新型细胞间通信途径.
确定黑色素体转移在黑色素瘤进展中的作用.
探索黑色素体介导的沟通对巨细胞两极分化的影响.

主要方法:

在受体细胞内的黑色素体行为的表征.
通过角质细胞和纤维细胞向巨细胞转移黑色素的分析.
对巨细胞极化表型的评估.
研究AKT1转移及其下游影响 (VEGF分泌,mTOR信号传递).
在黑色素瘤患者样本中的相关性分析.

主要成果:

黑色素体在受体细胞内保持完整,可以作为"二手"EV转移.
黑色素体转移诱导巨细胞偏向向前瘤或前免疫类型的表型.
纤维细胞穿过的黑色素体携带AKT1,促进VEGF分泌和血管生成.
AKT1阳性巨细胞与黑色素瘤的攻击性相关.
免疫疗法不响应者表现出巨细胞中黑色素体标记物的丰富.

结论:

二手EV,特别是黑色素体,有助于转移性利基形成.
黑色素体介导的巨细胞多样化影响黑色素瘤的进展.
在巨细胞中准来自黑色素体的信号可能是黑色素瘤的治疗策略.

关键词:

血管新生的产生.细胞对细胞的转移异质性异质性异质性黑色素体是黑色素体的组成部分.瘤相关的巨细胞

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