来自头部和部癌的死细胞释放生物分子,这些生物分子激活了类似收费受体3的收费受体
Tea Vasiljevic1, Marko Tarle2,3, Koraljka Hat2
1Laboratory for Personalized Medicine, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia.
International journal of molecular sciences
|October 28, 2023
概括
死亡的头部和部状细胞癌释放生物分子,主要是dsRNA片段,激活托尔类受体3 (TLR3). 这些发现表明TLR3激动剂在瘤微环境中的潜在原源性作用.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 瘤缩在头部和部状细胞癌 (HNSCCs) 中很常见.
- 从死细胞瘤细胞释放的生物分子,包括损伤相关分子模式 (DAMPs),可以与托尔类受体 (TLRs) 相互作用.
- 由HNSCC死分子激活TLR3的作用在很大程度上仍未被探索.
研究的目的:
- 调查HNSCC死焦中的生物分子是否会激活托尔类受体3 (TLR3).
- 为了确定这些潜在的TLR3激动剂的性质.
- 评估患者获得的瘤液中TLR3激动剂的存在.
主要方法:
- 利用了为TLR3表达和性酸酶分泌而设计的记者细胞系.
- 将三个HNSCC细胞系暴露在各种刺激 (辐射,饥饿,缺氧,氧化应激) 中,以诱导死亡.
- 分析了来自HNSCC患者和小鼠瘤移植的死瘤液体,以检测TLR3激活物质.
- 评估了RNAase治疗和TLR3阻断抗体的影响.
主要成果:
- 这三个HNSCC细胞系都释放了激活TLR3.3的生物分子.
- 外部辐射是最有效的刺激,在细胞外囊中发现了激动剂.
- 在所有测试患者和小鼠瘤的死液中检测到TLR3刺激活性.
- 通过RNAase或TLR3阻断抗体,活性显著降低,表明dsRNA是主要的激动剂.
结论:
- 死亡的HNSCC细胞始终释放dRNA片段,激活TLR3.
- 这些内源性TLR3激动剂可能会在瘤微环境中产生原始原始效应.
- 这项研究验证了对死瘤流体的功能测试,以调查分子相互作用.
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