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.
Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China.
J Biotechnol. 2014 May 10;177:1-12. doi: 10.1016/j.jbiotec.2014.02.016. Epub 2014 Mar 4.
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.
癌症干细胞（CSCs）很可能是癌症复发和转移的原因。为了进一步阐明 CSCs 特征的机制，有必要开发有效的培养系统来培养和扩增 CSCs。在这项研究中，报告了一种基于藻酸盐凝胶（ALG）珠的三维（3D）培养系统，用于富集 CSCs。两种源自不同组织来源的细胞系分别被包裹在 ALG 珠中，并研究了 CSCs 的扩增情况。与二维（2D）培养相比，ALG 珠中具有 CSC 样表型的细胞比例显著增加。ALG 珠中的 CSC 相关基因表达水平高于 2D 培养。在 ALG 珠内培养后 CSC 比例的增加通过体内增强肿瘤发生进一步得到证实。此外，在 3D 培养的细胞中还观察到转移能力增强和更高的抗癌药物耐药性。此外，我们发现是缺氧通过在 ALG 珠中上调缺氧诱导因子（HIFs）来诱导 CSC 比例的增加。因此，ALG 珠是一种有效的 CSC 富集培养系统，可为 CSC 研究提供有用的平台，并促进针对 CSCs 的新型抗癌疗法的发展。
