title: Enrichment of cancer stem cell-like cells by culture in alginate gel beads.
abstract: Cancer stem cells (CSCs) are most likely the reason of cancer reoccurrence and metastasis. For further elucidation of the mechanism underlying the characteristics of CSCs, it is necessary to develop efficient culture systems to culture and expand CSCs. In this study, a three-dimensional (3D) culture system based on alginate gel (ALG) beads was reported to enrich CSCs. Two cell lines derived from different histologic origins were encapsulated in ALG beads respectively and the expansion of CSCs was investigated. Compared with two-dimensional (2D) culture, the proportion of cells with CSC-like phenotypes was significantly increased in ALG beads. Expression levels of CSC-related genes were greater in ALG beads than in 2D culture. The increase of CSC proportion after being cultured within ALG beads was further confirmed by enhanced tumorigenicity in vivo. Moreover, increased metastasis ability and higher anti-cancer drug resistance were also observed in 3D-cultured cells. Furthermore, we found that it was hypoxia, through the upregulation of hypoxia-inducible factors (HIFs) that occurred in ALG beads to induce the increasing of CSC proportion. Therefore, ALG bead was an efficient culture system for CSC enrichment, which might provide a useful platform for CSC research and promote the development of new anti-cancer therapies targeting CSCs.
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China; University of Chinese Academy of Sciences, 19A Yuquanlu, Beijing 100049, PR China.
authors.forename: Xiao-xi
authors.initials: XX
authors.lastname: Xu
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China; University of Chinese Academy of Sciences, 19A Yuquanlu, Beijing 100049, PR China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian 116023, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China; University of Chinese Academy of Sciences, 19A Yuquanlu, Beijing 100049, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China. Electronic address: sungw@dicp.ac.cn.
authors.forename: Guang-wei
authors.initials: GW
authors.lastname: Sun
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China. Electronic address: maxj@dicp.ac.cn.
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Ma
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: D000464:Alginates; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: Alginate gel bead; Cancer stem cell; Enrichment; Hypoxia-inducible factor; Three-dimensional culture