重编程
SOX2
同源盒蛋白纳米
干细胞
癌细胞
细胞生物学
诱导多能干细胞
化学
癌症干细胞
生物
细胞
癌症研究
癌症
胚胎干细胞
转录因子
生物化学
基因
遗传学
作者
Jun Suzuka,Masumi Tsuda,Lei Wang,Shinji Kohsaka,Karin Kishida,Shingo Semba,Hirokazu Sugino,Sachiyo Aburatani,Martin Frauenlob,Takayuki Kurokawa,Shinya Kojima,Toshihide Ueno,Yoshihiro Ohmiya,Hiroyuki Mano,Kazunori Yasuda,Jian Ping Gong,Shinya Tanaka
标识
DOI:10.1038/s41551-021-00692-2
摘要
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. A double-network hydrogel can rapidly reprogramme differentiated tumour cells into cancer stem cells that display elevated tumorigenicity in vivo.
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