乳酸是乳腺癌细胞攻击性的主要推动者
Maitham A Khajah1, Sarah Khushaish1, Yunus Luqmani2
1Department of Pharmacology and Therapeutics, College of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
Cancers
|June 13, 2025
概括
乳酸盐通过改变表皮-介质细胞转换 (EMT) 标记物来影响乳腺癌细胞的运动. 抑制乳酸脱酶 (LDH) 或减少乳酸减少癌细胞的运动性,提供潜在的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 癌细胞中乳酸脱酶 (LDH) 活性升高和乳酸生产与患者预后不佳相关.
- 雌激素受体阴性 (ER) 乳腺癌细胞的LDH/乳酸盐水平高于ER阳性 (ER+) 细胞.
- 乳酸盐或酸盐补充剂增强了ER+细胞的运动性,而LDHB基因淘汰 (KO) 或LDH抑制剂降低了ER-乳腺癌细胞的运动性.
研究的目的:
- 阐明乳酸对乳腺癌细胞运动的调节背后的分子机制.
- 研究LDHBKO和LDH抑制剂对乳腺癌细胞行为的影响.
主要方法:
- 使用siRNA.RNA进行基因淘汰 (KO).
- 通过蛋白质组概况器人类XL瘤学阵列进行蛋白质组概况.
- 通过西方斑点和免疫光学验证.
主要成果:
- 乳酸补充剂在ER+细胞中增加了维门,N-cadherin和牛表达,同时降低了JAM-A,E-cadherin和nectin-4.
- 在ER细胞中的LDHBKO逆转了这种表达特征.
- LDHB KO或LDH抑制剂降低了ER细胞中IL-6,IL-8和MMP-2的表达.
- 在不同ER细胞系中观察到LDHBKO与PECAM-1,CCL20和ENPP-2的差异调节.
结论:
- 乳酸在调节乳腺癌细胞上皮层-介质细胞过渡 (EMT) 状态方面发挥着新的作用.
- 乳酸盐通过调节EMT,细胞因子,粘附分子,MMP-2和 nektin-4来显著促进乳腺癌细胞运动.
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