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通过激活FGFR1-4受体通路介导的ICAM-1表达,FGF2驱动骨肉瘤转移

Yu-Ching Huang¹, Wei-Cheng Chen², Chen-Lin Yu³

¹Institute of Biomedical Sciences, MacKay Medical College, New Taipei City, Taiwan; Division of Spine Surgery, Department of Orthopedic Surgery, MacKay Memorial Hospital, Taipei, Taiwan.

Biochemical pharmacology

|October 13, 2023

概括

纤维细胞生长因子2 (FGF2) 通过增加细胞间粘附分子-1 (ICAM-1) 的表达,促进骨质肉瘤转移. 针对FGF2/FGFR信号通路可能为骨髓瘤患者提供新的治疗策略.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

骨肉瘤具有很高的转移潜力,转移病例的5年生存率很差.
了解转移机制对于开发向疗法至关重要.
纤维细胞生长因子2 (FGF2) 与各种癌症有关,但其在骨肉瘤中的作用尚不清楚.

研究的目的:

研究FGF2及其受体 (FGFRs) 在人类骨髓瘤转移中的作用.
确定FGF2影响骨髓瘤细胞行为的分子机制.
探索FGF2/FGFR信号作为潜在的治疗点.

主要方法:

在人类骨髓瘤组织中分析FGF2表达.
在实验室对用FGF2.2治疗的骨髓瘤细胞系进行了体外研究.
基因和蛋白质表达分析,包括FGFRs,ICAM-1和信号通路组件.
细胞迁移和侵入的功能性测试.
对FGF2和FGFRs进行基因淘汰实验.

主要成果:

在骨髓瘤中,FGF2过度表达,与肺转移相关.
FGF2治疗增加了骨髓瘤细胞迁移,入侵和ICAM-1表达.
FGFR1-4对抗性或下调抑制了FGF2-诱导的ICAM-1表达和细胞迁移.
FGF2信号激活了PLCβ/PKCα/c-Src通路,导致c-Jun核转位和AP-1激活.
通过c-Jun对ICAM-1的升级促进了骨髓瘤细胞迁移.
抑制内源性FGF2降低了ICAM-1表达和细胞迁移.

结论:

通过ICAM-1,FGF2/FGFR信号促进骨髓瘤转移.
这一途径代表了骨髓瘤的新型治疗点.
向FGF2/FGFR信号可能会抑制骨髓瘤细胞迁移和转移.

关键词:

在FGF2上.在FGFRs.在 ICAM-1 中,转移转移转移转移骨质肉瘤骨质肉瘤是什么

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