Rapid reprogramming of tumour cells into cancer stem cells on double-network hydrogels
Rapid reprogramming of tumour cells into cancer stem cells on double-network hydrogels
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DOI：
10.1038/s41551-021-00692-2
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发表时间：
2021-03-29
影响因子：
28.1
通讯作者：
Tanaka, Shinya
中科院分区：
文献类型：
--
作者：
Suzuka, Jun;Tsuda, Masumi;Tanaka, Shinya
双网络水凝胶可以快速将分化的肿瘤细胞重新编程为癌症干细胞，这些干细胞在体内表现出更高的致瘤性。由于罕见的循环癌症干细胞（CSC）对化疗和放疗具有抗性，因此可能会导致癌症复发。在这里，我们表明双网络水凝胶可以快速将分化的癌细胞重新编程为CSC。在用来自六种人类癌细胞系中的任一种的细胞或用从胶质母细胞瘤患者切除的脑癌细胞接种凝胶的24小时内，形成了表达升高水平的干性基因Sox 2、Oct 3/4和Nanog的球体。在双网络凝胶上培养的人脑癌细胞和免疫缺陷小鼠颅内注射导致比在单网络凝胶上培养的脑癌细胞更高的致瘤性。我们还表明，双网络凝胶诱导酪氨酸激酶的磷酸化，凝胶诱导的CSC从原发性脑癌细胞被根除的血小板源性生长因子受体的抑制剂，钙通道受体和蛋白质骨桥蛋白是必不可少的调节凝胶介导的诱导干细胞在脑癌细胞。
A double-network hydrogel can rapidly reprogramme differentiated tumour cells into cancer stem cells that display elevated tumorigenicity in vivo.Cancer recurrence can arise owing to rare circulating cancer stem cells (CSCs) that are resistant to chemotherapies and radiotherapies. Here, we show that a double-network hydrogel can rapidly reprogramme differentiated cancer cells into CSCs. Spheroids expressing elevated levels of the stemness genes Sox2, Oct3/4 and Nanog formed within 24 h of seeding the gel with cells from any of six human cancer cell lines or with brain cancer cells resected from patients with glioblastoma. Human brain cancer cells cultured on the double-network hydrogel and intracranially injected in immunodeficient mice led to higher tumorigenicity than brain cancer cells cultured on single-network gels. We also show that the double-network gel induced the phosphorylation of tyrosine kinases, that gel-induced CSCs from primary brain cancer cells were eradicated by an inhibitor of the platelet-derived growth factor receptor, and that calcium channel receptors and the protein osteopontin were essential for the regulation of gel-mediated induction of stemness in brain cancer cells.