title: Niche Mimicking for Selection and Enrichment of Liver Cancer Stem Cells by Hyaluronic Acid-Based Multilayer Films.
abstract: Cancer stem cells (CSCs) represent a subpopulation of tumor cells that exhibit capacities for self-renewal, tumor initiation, disease relapse or metastasis, and resistance to chemotherapy and radiotherapy. However, the major obstacle associated with the use of CSCs is the difficulty in their isolation and enrichment. According to recent studies, CSCs share similar properties with normal stem cells, and it has been observed that hyaluronan (HA) plays a key factor in CSCs niches and that HA-mediated CD44 interaction promotes tumor progression. Therefore, HA-based multilayer films were used to fabricate sequential surface properties variation and to mimic CSC niches. A quartz crystal microbalance was used to investigate the layer-by-layer adsorption of PAH/HA multilayer films. Colony formation was observed on a series of poly(allylamine hydrochloride) PAH/HA multilayer films, and cytotoxicity and cell viability were evaluated by MTT, LDH and live/dead assay. It was observed that the cells isolated from (PAH/HA)3 displayed the best colony formation ability and that the expression of CD133/CD44 double positive cells was up-regulated to approximately 70% after 7 days of culture. Furthermore, the cells isolated from (PAH/HA)3 displayed higher chemo-resistance than the control group. The stem-cell-related genes expression of selected cells from (PAH/HA)3 after 7 days of culture was significantly different from that of the control group. In conclusion, this study provides a label-free selection and enrichment system that could serve as a new strategy for the future development of CSC selection and drug evaluation in cancer therapy.
authors.affiliation: Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University , No. 259, Wenhua First Road, Guishan District, Taoyuan 33302, Taiwan.
authors.forename: I-Chi
authors.initials: IC
authors.lastname: Lee
authors.affiliation: Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University , No. 259, Wenhua First Road, Guishan District, Taoyuan 33302, Taiwan.
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Chuang
authors.affiliation: Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University , No. 259, Wenhua First Road, Guishan District, Taoyuan 33302, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Wu
mesh_terms: D000071916:AC133 Antigen; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry; D058525:Quartz Crystal Microbalance Techniques; D013499:Surface Properties; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000071916:AC133 Antigen; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; D011073:Polyamines; C063994:polyallylamine; D004317:Doxorubicin; D006820:Hyaluronic Acid
keywords: CD44; PEM films; cancer stem cells; drug resistance; hyaluronan (HA); label-free selection