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Autocrine and Paracrine Interactions between Multiple Myeloma Cells and Bone Marrow Stromal Cells by Growth Arrest-specific Gene 6 Crosstalk with Interleukin-6

Research Project

Project/Area Number 16K19583
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionFukushima Medical University

Principal Investigator

Furukawa Miki  福島県立医科大学, 医学部, 助手 (80722537)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords多発性骨髄腫 / Gas6 / IL-6 / 骨髄間質細胞 / アポトーシス / ICAM-1
Outline of Final Research Achievements

We screened molecules differentially expressed in bone marrow cells of multiple myeloma (MM) patients using microarray analysis, which revealed significant upregulation of Gas6. Gas6 was overexpressed in the bone marrow of MM patients and in various MM cell lines. Plasma concentrations of Gas6 quantified using ELISA were significantly increased in symptomatic MM patients. MTT cell proliferation assay showed that Gas6 induced cell proliferation of MM cells. Analysis of apoptosis by flow-cytometry showed that Gas6 inhibited apoptosis of MM cells. Furthermore, conditioned medium from human marrow stromal cells increased Gas6 production into culture supernatants of MM cells, indicating that the interaction between MM cells and bone marrow stromal cells enhanced Gas6 secretion, which stimulated cell proliferation and inhibited apoptosis in MM cells. Our findings provide evidence that gas6 contributes to MM progression in both autocrine and paracrine manners.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2017 2016 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] Autocrine and Paracrine Interactions between Multiple Myeloma Cells and Bone Marrow Stromal Cells by Growth Arrest-specific Gene 6 Cross-talk with Interleukin-6.2017

    • Author(s)
      Furukawa M, Ohkawara H, Ogawa K, Ikeda K, Ueda K, Shichishima-Nakamura A, Ito E, Imai JI, Yanagisawa Y, Honma R, Watanabe S, Waguri S, Ikezoe T, Takeishi Y
    • Journal Title

      The Journal of biological chemistry

      Volume: 292 Issue: 10 Pages: 4280-4292

    • DOI

      10.1074/jbc.m116.733030

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Autocrine and Paracrine Interactions between Multiple Myeloma Cells and Bone Marrow Stromal Cells by Growth Arrest-specific Gene 6 Cross-talk with Interleukin-6.2017

    • Author(s)
      Furukawa M, Ohkawara H, Ogawa K, Ikeda K, Ueda K, Shichishima-Nakamura A, Ito E, Imai JI, Yanagisawa Y, Honma R, Watanabe S, Waguri S, Ikezoe T, Takeishi Y.
    • Journal Title

      J Biol Chem.

      Volume: 292(10) Pages: 4280-4292

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] A critical role of growth arrest-specific gene 6 in the pathogenesis of HSCT-associated thrombotic microangiopathy.2017

    • Author(s)
      4.Sho Takeyasu, Hiroshi Ohkawara, Koichiro Fukuchi, Wang Xiangmin, Koki Ueda, Kazuhiko Ikeda, Kazuei Ogawa,Takayuki Ikezoe.
    • Organizer
      第79回日本血液学会学術集会 (2017.10.20東京) 優秀ポスター賞受賞
    • Related Report
      2017 Annual Research Report
  • [Presentation] Autocrine and paracrine interactions by Gas 6 signaling pathways via IL-6 between MM cells and BMSCs.2016

    • Author(s)
      Miki Furukawa, Hiroshi Ohkawara, Kazuhiko Ikeda, Koki Ueda, Akiko Shichishima-Nakamura, Emi Ito, Jun-ichi Imai, Yuka Yanagisawa, Reiko Honma, Shinya Watanabe, Satoshi Waguri, Kazuei Ogawa, Yasuchika Takeishi.
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Remarks] 福島県立医科大学血液内科学講座 研究内容

    • URL

      https://www.fmu.ac.jp/home/hemato/kenkyu.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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