结肠直肠癌细胞的入侵和功能性质取决于周围瘤细胞外基质
Marco Franchi1, Konstantinos-Athanasios Karamanos2, Concettina Cappadone3
1Department for Life Quality Studies, University of Bologna, 47900 Rimini, Italy.
Biomedicines
|July 29, 2023
概括
细胞外矩阵的组成和时间影响结直肠癌细胞入侵. I型原蛋白特别改变了对药物敏感和耐药的LoVo细胞行为,促进了对耐药细胞的入侵.
科学领域:
- 癌症生物学 癌症生物学
- 细胞外矩阵研究 细胞外矩阵研究
- 细胞入侵的动力学
背景情况:
- 瘤微环境 (TME) 显著影响结直肠癌 (CRC) 细胞行为.
- 细胞外矩阵 (ECM) 组件及其物理特性是癌细胞入侵的关键调节器.
研究的目的:
- 为了研究不同ECM基质对LoVo结直肠癌细胞入侵的时空效应.
- 为了比较对多克索鲁比敏感 (LoVo-S) 和抗多克索鲁比 (LoVo-R) 细胞在Matrigel和I型原蛋白上的行为.
主要方法:
- 细胞培养在Matrigel和I型原蛋白上3小时和24小时.
- 对表皮细胞转化为介质酶 (EMT) 标记物,矩阵降解酶 (MMP-2) 和细胞形态学的分析.
- 技术包括RT-qPCR,西斑和扫描电子显微镜.
主要成果:
- 随着时间的推移,基因表达通常会下降,但在I型原蛋白上有显著的例外.
- I型原蛋白诱导了LoVo-S细胞MMP-2的显著减少,但LoVo-R细胞显著增加.
- 洛沃-S细胞采用了上皮表型,而洛沃-R细胞显示了具有侵袭性表型的侵袭性表型.
结论:
- 基质类型和培养时间对药物敏感性和耐药性CRC细胞的攻击性和形态有不同的影响.
- I型原蛋白的纤维结构差异调节LoVo-S和LoVo-R细胞入侵,减弱前者,并随着时间的推移增强后者的蛋白质溶解入侵.
- 未来的CRC研究应该考虑周围瘤ECM组成和TME动态,以了解对药物敏感和耐药细胞的行为.
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