独特的介质类神经纤维瘤干细胞形成NF1临床表型,由BDNF微环境控制
Jingcun Shi1, Zihui Yang2, Yuhan Zhang1
1Department of Oral and Maxillofacial Surgery - Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Translational oncology
|December 2, 2023
概括
神经纤维瘤类型I (NF1) 涉及由大脑衍生神经营养因子 (BDNF) 影响的中介细胞样神经纤维瘤干细胞 (MNSCs). 针对BDNF可能为NF1管理提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 干细胞生物学 干细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 神经纤维瘤I型 (NF1) 的特征是由于NF1基因突变引起的多样化的临床表现.
- 瘤微环境在NF1发病过程中的作用尚未得到充分理解.
- 研究瘤干细胞及其微环境对于NF1管理至关重要.
研究的目的:
- 在NF1瘤中识别和表征一种新的干细胞子组.
- 探索NF1.1中瘤微环境的表型和治疗相关性.
- 阐明大脑衍生神经营养因子 (BDNF) 在NF1瘤发育中的作用.
主要方法:
- 从NF1患者中分离和培养瘤干细胞 (TSC).
- 流细胞计,差异化检测,以及体内瘤发生研究以鉴定TSC的特征.
- 免疫组织化学,ELISA和西部斑块分析BDNF表达和信号通路 (TrkB/p38 MAPK).
主要成果:
- 鉴定具有自我更新,分化和瘤生成潜力的中细胞类神经纤维瘤干细胞 (MNSCs).
- 来自同一患者不同瘤部位的MNSC的特定部位能力的演示.
- 有证据表明,BDNF激活了MNSC中的TrkB/p38 MAPK通路,从而影响瘤表型.
结论:
- BDNF调节MNSCs,控制NF1中的瘤表型,特别是在头部和干部区域之间.
- BDNF 中和抗体抑制MNSCs和p38 MAPK通路.
- 针对BDNF的疗法代表了管理NF1.1的有希望的策略.
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