Suppressed Migration and Enhanced Cisplatin Chemosensitivity in Human Cancer Cell Lines by Tuning the Molecular Mobility of Supramolecular Biomaterials
Suppressed Migration and Enhanced Cisplatin Chemosensitivity in Human Cancer Cell Lines by Tuning the Molecular Mobility of Supramolecular Biomaterials
复制标题
通过调节超分子生物材料的分子迁移率抑制人类癌细胞系的迁移并增强顺铂化学敏感性
DOI：
10.1002/mabi.202200438
复制
发表时间：
2022
影响因子：
4.6
通讯作者：
Yui Nobuhiko
中科院分区：
文献类型：
--
作者：
Hakariya Masahiro;Arisaka Yoshinori;Masuda Hiroki;Yoda Tetsuya;Iwata Takanori;Yui Nobuhiko
癌细胞识别从周围微环境传递的物理线索，并相应地改变迁移和化学敏感性。具有可调物理性质的细胞粘附性生物材料有助于理解癌细胞反应和开发新的癌症治疗方法。此前，据报道，具有分子移动性的聚轮烷基表面通过与yes相关的蛋白（雅普）相关的信号通路有效地调节细胞功能。在本研究中，研究了聚轮烷表面的分子迁移率对肺癌（A549）、胰腺癌（BxPC-3）和乳腺癌的迁移和化疗敏感性的影响。（MDA-MB-231）细胞系，并且发现在低迁移率表面上促进粘附的A549和BxPC-3细胞的细胞铺展和核雅普易位，表明癌细胞响应分子移动性改变其亚细胞雅普定位。此外，低迁移率表面比高迁移率表面更能抑制细胞迁移。此外，低迁移率表面比高迁移率表面更大程度地促进每种癌细胞系的顺铂化学敏感性。这些结果表明，聚轮烷表面的分子流动性抑制细胞迁移，并通过雅普在癌细胞中的亚细胞易位增强化疗敏感性。因此，基于聚轮烷的生物界面可以成为阐明癌细胞迁移和化疗耐药机制的新平台。
Cancer cells recognize physical cues transmitted from the surrounding microenvironment, and accordingly alter the migration and chemosensitivity. Cell adhesive biomaterials with tunable physical properties can contribute to the understanding of cancer cell responses, and development of new cancer therapies. Previously, it was reported that polyrotaxane‐based surfaces with molecular mobility effectively modulate cellular functions via the yes‐associated protein (YAP)‐related signaling pathway. In the present study, the impact of molecular mobility of polyrotaxane surfaces on the migration and chemosensitivity of lung (A549), pancreatic (BxPC‐3), and breast cancer (MDA‐MB‐231) cell lines is investigated, and it is found that the cellular spreading of adherent A549 and BxPC‐3 cells and nuclear YAP translocation are promoted on low‐mobility surfaces, suggesting that cancer cells alter their subcellular YAP localization in response to molecular mobility. Furthermore, low‐mobility surfaces suppress cellular migration more than high‐mobility surfaces. Additionally, low‐mobility surfaces promote the cisplatin chemosensitivity of each cancer cell line to a greater extent than high‐mobility surfaces. These results suggest that the molecular mobility of polyrotaxane surfaces suppresses cellular migration and enhances chemosensitivity via the subcellular translocation of YAP in cancer cells. Biointerfaces based on polyrotaxanes can thus be a new platform for elucidating cancer cell migration and chemoresistance mechanisms.