Nat Commun:细胞外基质和适应性粘附动力学共同驱动卵巢癌的化疗抗性

2021-06-30 xiaozeng MedSci原创

肿瘤微环境(TME)中的细胞外基质(ECM)衍生的生化和生物力学因素对癌细胞的转移和治疗抗性至关重要。

肿瘤微环境(TME)中的细胞外基质(ECM)衍生的生化和生物力学因素对癌细胞的转移和治疗抗性至关重要。ECM作为一个动态复杂的分子网络,其具有独特的生化和结构特征。

ECM能够调控癌细胞的形态、侵袭、存活和生长。在癌症发生发展过程中,TME在生化成分和生物力学特性方面均会发生重大变化。然而,其对疾病的转移和化疗抗性的具体影响仍未完全了解。

在该研究中,研究人员发现,顺铂化疗会通过逐渐的改变癌细胞内在粘附信号和细胞周围ECM来增强化疗抗性。通过分析HGSC(高级别浆液性卵巢癌)的转录组和组织学,研究人员描述了化疗前后原发肿瘤和不同转移部位的纤维化ECM的异质性。

化疗后HGSCs表现出强大的ECM信号

在系统ECM筛选到基于胶原的2D和3D细胞培养模型中,研究人员证实特定的ECM底物和刚度均通过FAK和β1整合素-pMLC-YAP信号增强对顺铂治疗的抵抗性以及DNA损伤诱导的细胞凋亡。在转移性HGSC周围的这些底物中,COL6能够被化疗上调并增强复发的药物抗性。

ECM硬度的增加保护HGSC细胞抵抗顺铂治疗

总而言之,该研究结果将基质粘附识别为一种适应性反应,该研究也揭示了ECM通路靶向基质和肿瘤的相关机制。


原始出处:

Pietilä, E.A., Gonzalez-Molina, J., Moyano-Galceran, L. et al. Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance. Nat Commun 12, 3904 (23 June 2021).

 



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    2022-03-08 liuli5079
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    2022-01-29 yige2012
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