A new therapeutic strategy for multiple myeloma by targeting senescence of bone marrow microenvironment

• Project/Area Number: 15K09465
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Tohoku University
• Principal Investigator: Kanehira Masahiko 東北大学, 大学病院, 助教 (90374941)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: リゾホスファチジン酸 / 間葉系幹細胞 / 多発性骨髄腫 / 細胞老化 / 骨髄腫細胞 / オートタキシン

Outline of Final Research Achievements

It has widely been known that mutual crosstalk between myeloma cells and mesenchymal stromal cells (MSCs) in bone marrow is important for progression of multiple myeloma. In this study, we clearly demonstrated that lysophosphatidic acid (LPA), a kind of lipid mediators, drastically changes phenotypes of MSCs, namely, myeloma-supportive or myeloma-suppressive. From the results by gene silencing of MSCs using siRNA, signaling via LPA receptor subtype 1 (LPA1) and 3 (LPA3) modulates cellular senescence of MSCs positively and negatively, respectively, and also regulated proliferation of myeloma cells positively and negatively, respectively. This study produced clear evidence toward etiology of multiple myeloma that its incidence rate and severity proportionally increase with aging.

Research Products

• [Journal Article] Animal ethics and welfare education in wet-lab training can foster residents’ ethical values toward life (2017)
  • Author(s): Iki Y, Ito T, Kudo K, Noda M, Kanehira M, Sueta T, Miyoshi I, Kagaya Y, Okada Y, Unno M
  • Journal Title: Experimental Animals Volume: 66 Issue: 4 Pages: 313-320
  • DOI: 10.1538/expanim.17-0026
  • NAID: 130006187189
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed
• [Journal Article] An Lysophosphatidic Acid Receptors 1 and 3 Axis Governs Cellular Senescence of Mesenchymal Stromal Cells and Promotes Growth and Vascularization of Multiple Myeloma. (2017)
  • Author(s): Kanehira M, Fujiwara T, Nakajima S, Okitsu Y, Onishi Y, Fukuhara N, Ichinohasama R, Okada Y, Harigae H.
  • Journal Title: Stem Cells. Volume: 35 Issue: 3 Pages: 739-753
  • DOI: 10.1002/stem.2499
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cells attenuate ischemia-reperfusion injury after prolonged cold ischemia in a mouse model of lung transplantation: a preliminary study. (2017)
  • Author(s): Watanabe T, Hoshikawa Y, Ishibashi N, Suzuki H, Notsuda H, Watanabe Y, Noda M, Kanehira M, Ohkouchi S, Kondo T, Okada Y.
  • Journal Title: Surg Today Volume: 47 Issue: 4 Pages: 425-425
  • DOI: 10.1007/s00595-016-1391-8
  • Peer Reviewed