Regulation of Hodgkin lymphoma cell differentiation by reactive oxygen species
| Project/Area Number |
17K08728
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ホジキンリンパ腫 / 分化 / 活性酸素 / HIF-1 / 細胞分化 / 低酸素誘導因子 / 幹細胞 / 活性酸素種 |
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| Outline of Final Research Achievements |
In this study we examined molecular mechanisms underlying in the differentiation of Hodgkin lymphoma (HL) cells. We found that hydrogen peroxide induces H and RS-like cells in HL cell lines, however this treatment induces cell death in unrelated lymphoid cell lines. Intracellular reactive oxygen species (ROS) of HL cell lines are low in immature cells compared to differentiated cells of HL cell lines. Microarray analyses revealed the enrichment of upregulated genes under hypoxic conditions in the immature cells of HL cell lines. Hypoxia inducible factor (HIF)-1α and its downstream molecule, heme oxygenase-1 (HO-1), a scavenger of ROS was preferentially expressed in the immature cells. HIF-1α and HO-1 inhibited differentiation of HL cell lines. These results indicate that induction of HO-1 via HIF-1α inhibits differentiation of immature HL cells by a reduction of ROS and its breakdown might trigger HL cell differentiation by accumulation of intracellular ROS.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでHodgkinリンパ腫（HL）は大型のHodgkinおよびReed-Sternberg(H-RS)細胞を特徴とし、これらの細胞が腫瘍細胞として増殖すると考えられてきた。本研究はHL細胞にはがん幹細胞様の小型細胞集団が存在、中型細胞を経てH-RS細胞へ分化するという新しい視点に立ち、そのメカニズムが低酸素環境の模倣と活性酸素の制御にあることを明らかにした。本研究の成果は、がん細胞の分化機構を標的とした新しい治療法の開発につながると考えられる。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Jietacins, azoxy natural products, as novel NF-kB inhibitors: discovery, synthesis, biological activity, and mode of action2019
Author(s)
Mariko Watanabe, Akihiro Sugawara, Yoshihiko Noguchi, Tomoyasu Hirose, Satoshi Omura, Toshiaki Sunazuka, Ryouichi Horie
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Journal Title
Eur. J. Med. Chem.
Volume: 178
Pages: 636-647
DOI
Related Report
Peer Reviewed
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[Journal Article] Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma.2018
Author(s)
Higuchi H, Yamakawa N, Imadome KI, Yahata T, Kotaki R, Ogata J, Kakizaki M, Fujita K, Lu J, Yokoyama K, Okuyama K, Sato A, Takamatsu M, Kurosaki N, Alba SM, Azhim A, Horie R, Watanabe T, Kitamura T, Ando K, Kashiwagi T, Matsui T, Okamoto A, Handa H, Kuroda M, Nakamura N, Kotani A.
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Journal Title
Blood
Volume: 131
Issue: 23
Pages: 2552-2567
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Relationship between response to lusutrombopag and splenic volume.2018
Author(s)
Uojima H, Arase Y, Itokawa N, Atsukawa M, Satoh T, Miyazaki K, Hidaka H, Sung JH, Kako M, Tsuruya K, Kagawa T, Iwakiri K, Horie R, Koizumi W.
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Journal Title
World J Gastroenterol.
Volume: 24
Issue: 46
Pages: 5271-5279
DOI
Related Report
Peer Reviewed
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