title: Chitosan promotes cancer progression and stem cell properties in association with Wnt signaling in colon and hepatocellular carcinoma cells.
abstract: Cancer stem cells (CSCs), a small population of cancer cells, have been considered to be the origin of cancer initiation, recurrence, and metastasis. Tumor microenvironment provides crucial signals for CSCs to maintain stem cell properties and promotes tumorigenesis. Therefore, establishment of an appropriate cell culture system to mimic the microenvironment for CSC studies is an important issue. In this study, we grew colon and hepatocellular carcinoma (HCC) cells on chitosan membranes and evaluated the tumor progression and the CSC properties. Experimental results showed that culturing cancer cells on chitosan increased cell motility, drug resistance, quiescent population, self-renewal capacity, and the expression levels of stemness and CSC marker genes, such as OCT4, NANOG, CD133, CD44, and EpCAM. Furthermore, we demonstrated that chitosan might activate canonical Wnt/β-catenin-CD44 axis signaling in CD44positivecolon cancer cells and noncanonical Wnt-STAT3 signaling in CD44negativeHCC cells. In conclusion, chitosan as culture substrates activated the essential signaling of CSCs and promoted CSC properties. The chitosan culture system provides a convenient platform for the research of CSC biology and screening of anticancer drugs.
authors.affiliation: niChe Lab for Stem Cell and Regenerative Medicine, Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Po-Hsiang
authors.initials: PH
authors.lastname: Chang
authors.affiliation: Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanagawa 236-0004, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sekine
authors.affiliation: niChe Lab for Stem Cell and Regenerative Medicine, Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan.|Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
authors.forename: Hsiao-Mei
authors.initials: HM
authors.lastname: Chao
authors.affiliation: Institute of Polymer Science and Engineering, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Shan-Hui
authors.initials: SH
authors.lastname: Hsu
authors.affiliation: niChe Lab for Stem Cell and Regenerative Medicine, Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Edward
authors.initials: E
authors.lastname: Chern
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D048271:Chitosan / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000071858:Epithelial Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D000924:Anticholesteremic Agents; C497483:CD44 protein, human; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D018960:Hyaluronan Receptors; D048271:Chitosan