title: A stem cell medium containing neural stimulating factor induces a pancreatic cancer stem-like cell-enriched population.
abstract: Cancer stem cells (CSCs) have been studied for their self-renewal capacity and pluripotency, as well as their resistance to anticancer therapy and their ability to metastasize to distant organs. CSCs are difficult to study because their population is quite low in tumor specimens. To overcome this problem, we established a culture method to induce a pancreatic cancer stem-like cell (P-CSLC)-enriched population from human pancreatic cancer cell lines. Human pancreatic cancer cell lines established at our department were cultured in CSC-inducing media containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), leukemia inhibitory factor (LIF), neural cell survivor factor-1 (NSF-1), and N-acetylcysteine. Sphere cells were obtained and then transferred to a laminin-coated dish and cultured for approximately two months. The surface markers, gene expression, aldehyde dehydrogenase (ALDH) activity, cell cycle, and tumorigenicity of these induced cells were examined for their stem cell-like characteristics. The population of these induced cells expanded within a few months. The ratio of CD24high, CD44high, epithelial specific antigen (ESA) high, and CD44variant (CD44v) high cells in the induced cells was greatly enriched. The induced cells stayed in the G0/G1 phase and demonstrated mesenchymal and stemness properties. The induced cells had high tumorigenic potential. Thus, we established a culture method to induce a P-CSLC-enriched population from human pancreatic cancer cell lines. The CSLC population was enriched approximately 100-fold with this method. Our culture method may contribute to the precise analysis of CSCs and thus support the establishment of CSC-targeting therapy.
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshimura
authors.affiliation: Department of Neurosurgery, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Tsunedomi
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Yoshitaro
authors.initials: Y
authors.lastname: Shindo
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Sou
authors.initials: S
authors.lastname: Matsukuma
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kanekiyo
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Molecular Pharmacology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kuramasu
authors.affiliation: Department of Ophthalmology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Sonoda
authors.affiliation: Department of Immunology and Cell Signaling Analysis, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tamada
authors.affiliation: Department of Molecular Physiology and Medical Bioregulation, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, Graduate School of Medicine, Keio University, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
mesh_terms: D045744:Cell Line, Tumor; D003470:Culture Media / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy
chemical_list: D003470:Culture Media; D036341:Intercellular Signaling Peptides and Proteins