Florczyk Stephen J, Kievit Forrest M, Wang Kui, Erickson Ariane E, Ellenbogen Richard G, Zhang Miqin
Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195.
Department of Neurological Surgery, University of Washington, Seattle, WA 98195.
J Mater Chem B. 2016 Oct 14;4(38):6326-6334. doi: 10.1039/C6TB01713D. Epub 2016 Aug 31.
Cancer stem cells are increasingly becoming a primary target for new cancer treatment development. The ability to study their transient behavior in vitro will provide the opportunity for high-throughput testing of more effective therapies. We have previously demonstrated the use of 3D porous chitosan-alginate (CA) scaffolds to promote cancer stem-like cell (CSC) proliferation and enrichment in glioblastoma. Here we use 3D porous CA scaffolds to promote cancer stem-like cell enrichment in cell lines from prostate, liver, and breast cancers, and investigate the proliferation, morphology, and gene expressions of cells cultured in CA scaffolds as compared to 2D controls. The 3D CA scaffold cultures for all three cancer types showed reduced proliferation, formation of tumor spheroids, and increased expression of CSC associated mark genes (CD133 and NANOG), as opposed to monolayers. Additionally, we present a putative mechanism for the cancer stem-like cell enrichment on CA scaffolds. This study demonstrates that the cancer stem-like cell enrichment in CA scaffolds is a robust process that is not restricted to particular cancer types.
癌症干细胞正日益成为新型癌症治疗研发的主要靶点。在体外研究其瞬时行为的能力将为更有效疗法的高通量测试提供契机。我们之前已证明使用三维多孔壳聚糖-海藻酸盐（CA）支架可促进胶质母细胞瘤中癌症干细胞样细胞（CSC）的增殖和富集。在此，我们使用三维多孔CA支架促进前列腺癌、肝癌和乳腺癌细胞系中癌症干细胞样细胞的富集，并与二维对照相比，研究在CA支架中培养的细胞的增殖、形态和基因表达。与单层培养相反，所有三种癌症类型的三维CA支架培养均显示增殖减少、肿瘤球体形成以及CSC相关标记基因（CD133和NANOG）表达增加。此外，我们提出了一种关于CA支架上癌症干细胞样细胞富集的推测机制。本研究表明，CA支架中癌症干细胞样细胞的富集是一个强大的过程，并不局限于特定的癌症类型。
