2008 Fiscal Year Final Research Report
Cell adhesion-mediated drug resistance of myeloma cells via Wnt/Rho signaling pathway
| Project/Area Number |
19591124
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
MASAYOSHI Kobune Sapporo Medical University, 医学部, 講師 (90336389)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Junji 札幌医科大学, 医学部, 教授 (20244345)
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| Project Period (FY) |
2007 – 2008
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| Keywords | 骨髄腫 / Wnt / Rhoシグナル / 骨髄間質細胞 / 薬剤耐性 |
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| Research Abstract |
近年、血液腫瘍に対する化学療法や分子標的療法は目覚ましい進歩をとげたが、骨髄腫や難治性白血病などでは、腫瘍細胞を骨髄から完全に排除することが出来ず、治癒を得ることは困難である。その理由として、骨髄間質と腫瘍細胞の相互作用で惹起される薬剤耐性の関与が想定されているが、その分子機構は明らかとなっていない。本研究ではWntが細胞接着や増殖を制御することに着目し、血液腫瘍におけるWntの発現と抗癌剤耐性への関与を解析した。各種細胞株でのWntの発現を検討した結果、骨髄腫細胞株においてWnt3の発現が検出され、その発現量は骨髄腫細胞のstroma細胞への接着性と相関していた。高接着性の骨髄腫細胞株の共培養でDoxorubicnに対する薬剤耐性は、stroma細胞非存在下に比し有意に上昇したが、抗integrinβ1、Wnt inhibitorあるいはWnt3 siRNAを用いることによって解除された。これらの結果より、骨髄腫において、Wnt3経路はintegrinβ1依存性薬剤耐性を惹起するために重要な役割をしており、新規治療の分子標的になる可能性が示唆された。
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[Journal Article] Late onset neutropenia and immunoglobulin suppression of the patients with malignant lymphoma following autologous stem cell transplantation with rituximab2009
Author(s)
Hirayama Y, Kohda K, Konuma Y, Hirata Y, Kuroda H, Fujimi Y, Shirao S, Kobune M, Takimoto R, Matsunaga T, Kato J
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Journal Title
Intern Med 48
Pages: 57-60
Peer Reviewed
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[Journal Article] Ex vivo large-scale generation of human red blood cells from cord blood CD34(+)cells by co-culturing with macrophages2008
Author(s)
Fujimi A, Matsunaga T, Kobune M, Kawano Y, Nagaya T, Tanaka I, Iyama S, Hayashi T, Sato T, Miyanishi K, Sagawa T, Sato Y, Takimoto R, Takayama T, Kato J, Gasa S, Sakai H, Tsuchida E, Ikebuchi K, Hamada H, Niitsu Y
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Journal Title
Int J Hematol 87
Pages: 339-350
Peer Reviewed
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[Journal Article] Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone2008
Author(s)
Sato Y, Murase K, Kato J, Kobune M, Sato T, Kawano Y, Takimoto R, Takada K, Miyanishi K, Matsunaga T, Takayama T, Niitsu Y
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Journal Title
Nat Biotechnol 26
Pages: 431-442
Peer Reviewed
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[Journal Article] Apoptosis supercedes necrosis in mitochondrial DNA-depleted Jurkat cells by cleavage of receptorinteracting protein and inhibition of lysosomal cathepsin2008
Author(s)
Sato T, Machida T, Takahashi S, Murase K, Kawano Y, Hayashi T, Iyama S, Takada K, Kuribayashi K, Sato Y, Kobune M, Takimoto R, Matsunaga T, Kato J, Niitsu Y
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Journal Title
J Immunol 181
Pages: 197-207
Peer Reviewed
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[Journal Article] Successful treatment of autoimmune pancreatitis complicated with autoimmune thrombocytopenia and interstitial pneumonia by prednisolone2008
Author(s)
Murase K, Matsunaga T, Hayashi T, Ishiwatari H, Araki N, Iyama S, Sato T, Kobune M, Takimoto R, Miyanishi K, Miyazaki T, Ikeda H, Kato J, Niitsu Y
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Journal Title
Intern Med 47
Pages: 1033-1038
Peer Reviewed
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[Journal Article] Wnt3/RhoA/ROCK signaling pathway is involved in adhesion-mediated drug resistance of multiple myeloma in an autocrine mechanism2007
Author(s)
Kobune M, Chiba H, Kato J, Kato K, Nakamura K, Kawano Y, Takada K, Takimoto R, Takayama T, Hamada H, Niitsu-Y
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Journal Title
Mol Cancer Ther 6
Pages: 1774-1784
Peer Reviewed
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[Journal Article] Iron/IRP-1-dependent regulation of mRNA expression for transferrin receptor, DMT1 and ferritin during human erythroid differentiation2007
Author(s)
Kato J, Kobune M, Ohkubo S, Fujikawa K, Tanaka M, Takimoto R, Takada K, Takahari D, Kawano Y, Kohgo Y, Niitsu Y
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Journal Title
Exp Hematol 35
Pages: 879-887
Peer Reviewed
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[Presentation] Interaction with human stromal cells enhances CXCR4 expression and engraftment of cord blood Lin-CD34-cells via Wnt signaling2008
Author(s)
Kobune M, Murase K, Iyama S, Sato T, Kikuchi S, Kawano Y, Takada K, Miyanishi K, Takimoto R, Kato J
Organizer
In : The 50th Annual Meeting of American Society of Hematology(Blood 2008 ; 112 : 2325a)
Place of Presentation
San Francisco, U.S.A.
Year and Date
20081206-09
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[Presentation] Hedgehog inhibitors reduce the survival and drug resistance in CD34+ leukemic cells2008
Author(s)
Kobune M, Murase K, Iyama S, Sato T, Takimoto R, Kikuchi S, Kawano Y, Takada K, Miyanishi K, Kato J
Organizer
In : The 50th Annual Meeting of American Society of Hematology(Blood 2008 ; 112 : 1611a)
Place of Presentation
San Francisco, U.S.A.
Year and Date
20081206-09
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[Presentation] Wnt3 signaling augments integrinβ1-dependent adhesion-mediated drug resistance of multiple myeloma in autocrine and paracrine manner2008
Author(s)
Kobune M, Murase K, Iyama S, Sato T, Takimoto R, Kawano Y, Kikuchi S, Takada K, Miyanishi K, Sato Y, Kato J
Organizer
In : The 50th Annual Meeting of American Society of Hematology(Blood 2008 ; 112 : 1698a)
Place of Presentation
San Francisco, U.S.A.
Year and Date
20081206-09
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