title: Adhesion-dependent growth of primary adult T cell leukemia cells with down-regulation of HTLV-I p40Tax protein: a novel in vitro model of the growth of acute ATL cells.
abstract: In order to better understand the biology of adult T cell leukemia (ATL), we aimed to establish a novel method, which allows the primary growth of ATL cells using a co-culture system with murine bone marrow-derived stromal cells, MS-5. ATL cells grew in close contact with MS-5 layers and formed so-called "cobblestone areas" (CAs) without the addition of IL-2. In clinical samples, eight of ten (80.0%) cases of acute or lymphoma type ATL cells formed CAs. The frequency of CA forming cells in ATL cells ranged from 0.03 to 1.04%. The morphology, immunophenotyping, and DNA analysis indicated that cells composing CA were compatible with ATL cells, and clonally identical to primary CD4-positive ATL cells. Furthermore, in ATL cells composing CA, the expression of p40Tax was down-regulated in transcriptional and translational level, while that of HTLV-I basic leucine zipper factor (HBZ) gene was comparable to the level of primary ATL cells, resembling expression pattern of proviral genes in in vivo ATL cells. By microarray analysis, several genes which coded products involved in cell-cell interaction, and cellular survival and proliferation, were differentially expressed in ATL cells composing CA compared with primary samples. In conclusion, our co-culture system allows for the first time the growth of primary ATL cells in vitro, and might be useful as an in vitro assay for biological and clinical studies to develop molecular targeting drugs against ATL.
authors.affiliation: Transfusion Service, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. agwkn@nagasaki-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Division of Hematology, Department of Internal Medicine, Saitama Medical School, Saitama, Japan.
authors.forename: Itsuro
authors.initials: I
authors.lastname: Jinnai
authors.affiliation: Department of Hematology, Molecular Medicine Unit, Atomic Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Usui
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sasaki
authors.affiliation: Department of Hematology, Molecular Medicine Unit, Atomic Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Tsukasaki
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugahara
authors.affiliation: Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hishikawa
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.affiliation: Division of Functional Genomics, Jichi Medical University, CREST, Japan Science and Technology Agency, Tochigi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
authors.affiliation: Transfusion Service, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.|Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
authors.affiliation: Department of Hematology, Molecular Medicine Unit, Atomic Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Tomonaga
mesh_terms: D000208:Acute Disease; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D016356:Gene Products, tax / Q000096:biosynthesis*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured
chemical_list: D016356:Gene Products, tax; C508594:IL2 protein, human; D007376:Interleukin-2; C514970:tax protein, Human T-lymphotrophic virus 1