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
| Autor: | Yasuaki Yamada, Tomoko Hata, Tetsuya Usui, Shimeru Kamihira, Hiroyuki Mano, Masao Tomonaga, Kazuhiro Nagai, Yuetsu Tanaka, Takehiko Koji, Kunihiro Tsukasaki, Itsuro Jinnai, Kazuyuki Sugahara, Daisuke Sasaki, Yoshitaka Hishikawa |
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| Rok vydání: | 2008 |
| Předmět: |
Stromal cell
Cell Survival viruses T-cell leukemia Down-Regulation Biology Models Biological Cell Line Mice Immunophenotyping Downregulation and upregulation immune system diseases hemic and lymphatic diseases parasitic diseases Cell Adhesion Tumor Cells Cultured Animals Humans Leukemia-Lymphoma Adult T-Cell Cell adhesion Cell Proliferation Oligonucleotide Array Sequence Analysis Human T-lymphotropic virus 1 Gene Expression Regulation Leukemic Cell growth Microarray analysis techniques Gene Expression Profiling hemic and immune systems Gene Products tax Hematology Virology Molecular biology Coculture Techniques In vitro Acute Disease Interleukin-2 |
| Zdroj: | International Journal of Hematology. 88:551-564 |
| ISSN: | 1865-3774 0925-5710 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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