RRC ID 69673
Author Suzuka J, Tsuda M, Wang L, Kohsaka S, Kishida K, Semba S, Sugino H, Aburatani S, Frauenlob M, Kurokawa T, Kojima S, Ueno T, Ohmiya Y, Mano H, Yasuda K, Gong JP, Tanaka S.
Title Rapid reprogramming of tumour cells into cancer stem cells on double-network hydrogels.
Journal Nat Biomed Eng
Abstract 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.
Volume 5(8)
Pages 914-925
Published 2021-8-1
DOI 10.1038/s41551-021-00692-2
PII 10.1038/s41551-021-00692-2
PMID 33782572
MeSH Animals Brain Neoplasms / metabolism Brain Neoplasms / pathology Cell Differentiation Cellular Reprogramming* ErbB Receptors / metabolism Gene Expression Regulation, Neoplastic / drug effects Glioblastoma / metabolism Glioblastoma / pathology Humans Hydrogels / chemistry* Hydrogels / pharmacology Mice Mice, SCID Neoplastic Stem Cells / cytology* Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / transplantation Osteopontin / genetics Osteopontin / metabolism Phosphorylation / drug effects Polymers / chemistry Signal Transduction / drug effects Signal Transduction / genetics Tumor Cells, Cultured
IF 18.952
Human and Animal Cells HSC-3(RCB1975) HeLa(RCB0007)