title: Isolation and characterization of cancer stem-like side population cells in human oral cancer cells.
abstract: Recent studies suggest that cancer stem cells may be responsible for tumorigenesis and contribute to some individuals' resistance to cancer therapy. Some studies demonstrate that side population (SP) cells isolated from diverse cancer cell lines harbor stem cell-like properties; however, there are few reports examining the role of SP cells in human oral cancer. To determine whether human oral cancer cell lines contain a SP cell fraction, we first isolated SP cells by fluorescence activated cell sorting, followed by culturing in serum-free medium (SFM) using the SCC25 tongue cancer cell line, so that SP cells were able to be propagated to maintain the CSC property. Differential expression profile of stem cell markers (ABCG2, Oct-4 and EpCAM) was examined by RT-PCR in either SP cells or non-SP cells. Growth inhibition by 5-FU was determined by the MTT assay. Clonogenic ability was evaluated by colony formation assay. SCC25 cells contained 0.23% SP cells. The fraction of SP cells was available to grow in SFM cultures. SP cells showed higher mRNA expression of stem cell markers (ABCG2, Oct-4 and EpCAM) as compared with non-SP cells. Moreover, SP cells demonstrated more drug resistance to 5-FU, as compared with non-SP cells. The clone formation efficiency of SP cells was significantly higher than non-SP cells at an equal cell number (P<0.01). We isolated cancer stem-like SP cells from an oral cancer cell line. SP cells possessed the characteristics of cancer stem cells, chemoresistance, and high proliferation ability. Further characterization of cancer stem-like SP cells may provide new insights for novel therapeutic targets.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. syana@nagasaki-u.ac.jp
authors.forename: Souichi
authors.initials: S
authors.lastname: Yanamoto
authors.forename: Goro
authors.initials: G
authors.lastname: Kawasaki
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Izumi
authors.initials: I
authors.lastname: Yoshitomi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kawano
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Yonezawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Rokutanda
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Naruse
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umeda
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D000071858:Epithelial Cell Adhesion Molecule; D005434:Flow Cytometry / Q000379:methods; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D058985:Side-Population Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014062:Tongue Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D009363:Neoplasm Proteins; D050814:Octamer Transcription Factor-3; D005472:Fluorouracil