基底细胞粘附分子 (BCAM) 通过膜信号传递促进介质细胞到介质细胞的过渡和瘤血管生成
Suresh Sivakumar1, Sonja Lieber1,2, Raimund Dietze1
1Translational Oncology, Center for Tumor Biology and Immunology (ZTI), Philipps University, Hans-Meerwein-Strasse 3, 35043, Marburg, Germany.
Cell communication and signaling : CCS
|March 14, 2025
概括
基底细胞粘附分子 (BCAM) 通过促进中细胞清除和血管生成,驱动卵巢癌转移. 向BCAM可能为卵巢癌治疗提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 基底细胞粘附分子 (BCAM) 的高表达是卵巢癌 (OC) 进展的标志.
- BCAM通过促进瘤细胞球状体在腹膜附着部位的中细胞清除来促进跨瘤细胞传播.
- 研究了BCAM在调解中皮细胞清除和其他转移前功能中的作用.
研究的目的:
- 为了研究BCAM如何调解 mesothelial 细胞清除.
- 探索其他由BCAM驱动的前转移性功能.
- 了解BCAM对瘤细胞分泌和中细胞表型的影响.
主要方法:
- 亲和蛋白质组学,RNA测序 (批量和单细胞),显微镜 (活细胞和多光子).
- 在体外的生物化学和功能测试,以及小鼠瘤模型.
- 通过宫外过度表达,可诱导表达和可溶性BCAM治疗操纵BCAM.
主要成果:
- BCAM增强了细胞因子 (AREG,CXCL,FGF2,TGFB2,VEGF) 的分泌,影响了细胞运动,介酶分化和血管生成.
- 由BCAM诱导的细胞因子触发了中体-中体过渡 (MMT),增强中体细胞运动性和瘤球状部位的清除.
- 在实验室中,BCAM促进了内皮管的形成,在体内促进了瘤血管生成;MMT相关的转录变化在患者的脑内间皮细胞中与生存率差相关.
结论:
- 在卵巢癌转移中发现了BCAM诱导的分泌体的新功能.
- BCAM对MMT的影响可能会促进微转移的启动,而新血管生成则支持瘤的生长.
- 鉴于其不良的临床关联,BCAM代表了卵巢癌的潜在治疗标.
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