DACH1 调节巨细胞激活和瘤进展在下甲状腺状细胞癌
Wenjing Li1,2, Licheng Xu1,2, Jing Cao1
1Department of Otorhinolaryngology, Head and Neck Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Immunology
|May 27, 2023
概括
Dachshund家族转录因子1 (DACH1) 通过抑制瘤相关的巨细胞 (TAM) 极化和瘤细胞入侵来抑制下癌的进展. 降低的DACH1表明预后不佳,表明其作为治疗点的潜力.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 免疫学 免疫学 免疫学
背景情况:
- 大犬家族转录因子1 (DACH1) 在各种癌症中表现出瘤抑制作用.
- DACH1在下喉平细胞癌 (HPSCC) 的功能及其与瘤微环境 (TME) 的相互作用仍然不清楚.
- 瘤相关巨细胞 (TAMs) 在通过细胞交叉声交换的HPSCC进展中发挥着至关重要的作用.
研究的目的:
- 研究DACH1在HPSCC中的作用.
- 在HPSCC TME中阐明DACH1的功能机制.
- 评估DACH1作为HPSCC的潜在预后标志物和治疗点.
主要方法:
- 定量实时PCR和免疫组织化学 (IHC) 检测DACH1,CD86和CD163在HPSCC组织中的表达.
- 细胞增殖,迁移和入侵分析 (殖民地形成,Transwell,EdU).
- 染色体免疫沉定量PCR (ChIP-qPCR) 和双露西法酶记者试验证实DACH1-IGF-1相互作用;共同培养试验评估巨细胞极化.
主要成果:
- 在HPSCC组织中,DACH1表达减少,与患者预后不佳相关.
- 减少的DACH1与增加的CD163+TAMs (M2类) 和减少的CD86+TAMs (M1类) 相关.
- 通过Akt/NF-κB/MMP2/9信号传递促进了HPSCC细胞的增殖,迁移和入侵,并通过IGF-1/IGF-1R/JAK1/STAT3轴抑制了TAM极化.
结论:
- 在HPSCC中,DACH1作为瘤抑制剂,通过抑制癌细胞入侵和M2样TAM极化而起作用.
- IGF-1是DACH1的一个关键下游效应因子,调解其对TAM的影响.
- DACH1代表了一个有前途的治疗标和HPSCC的预后生物标志物.
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