Development of immunotherapy against the bone destructive tumor

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659946
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: The University of Tokushima
• Principal Investigator: HIASA Masahiro 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (90511337)
• Project Period (FY): 2011 – 2012
• Keywords: 破骨細胞 / 樹状細胞 / TACE / TIMP3

Research Abstract

Multiple myeloma (MM) generates devastating bone destruction. We recently reported that TNFα converting enzyme (TACE) expression in monocytes cleaved their surface M-CSF receptor (M-CSFR), which drastically disrupts osteoclastogenesis（Blood, 2009）. Because TACE activity is inhibited by TIMP3, we explored the role of BMSC-derived TIMP3 in monocytic differentiation into DC or OC in MM. This study clarified that TIMP3 over-produced in MM bone marrow microenvironment restores surface M-CSFR on monocytes to facilitate their downstream signaling, which causes extensive bone destruction and impaired DC differentiation in MM. TIMP3 may therefore become a novel target in the treatment of MM bone disease.

Research Products

• [Journal Article] KRN5500, a spicamycin derivative, exerts anti-myeloma effects through impairing both myeloma cells and osteoclasts (2012)
  • Author(s): Hirokazu Miki, Shingen Nakamura, Shuji Ozaki, A Oda, H Amou, Akishige Ikegame, Keiichiro Watanabe, Masahiro Hiasa, Q Cui, T Harada, Shiroh Fujii, A Nakano, Kumiko Kagawa, Kyoko Takeuchi, Ken-ichiro Yata, A Sakai, Masahiro Abe and Toshio Matsumoto
  • Journal Title: British Journal of Haematology Volume: Vol.155, No.3 Pages: 328--339
  • DOI: DOI:10.1111/j.1365-2141.2011.08844.x
  • Peer Reviewed
• [Journal Article] Small molecule antibody targeting HLA class I inhibits myeloma cancer stem cells by repressing pluripotency-associated transcription factors (2012)
  • Author(s): Akishige Ikegame, Shuji Ozaki, Daisuke Tsuji, T Harada, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, A Nakano, Kumiko Kagawa, Kyoko Takeuchi, Masahiro Abe, Keiichiro Watanabe, Masahiro Hiasa, N Kimura, Y Kikuchi, A Sakamoto, K Habu, M Endo, K Itoh, H Yamada-Okabe and Toshio Matsumoto
  • Journal Title: Leukemia
  • DOI: DOI:10.1038/leu.2012.78
  • Peer Reviewed
• [Journal Article] Delayed treatment with vitamin C and N-acetyl-L: -cysteine protects Schwann cells without compromising the anti-myeloma activity of bortezomib. (2011)
  • Author(s): Ayako Nakano, Masahiro Abe, Asuka Oda, Hiroe Amou, Masahiro Hiasa, Shingen Nakamura, Hirokazu Miki, Takeshi Harada, Shirou Fujii, Kumiko Kagawa, Kyoko Takeuchi, Takashi Watanabe, Shuji Ozaki and Toshio Matsumoto
  • Journal Title: International Journal of Hematology Volume: Vol.93, No.6 Pages: Vol.93, No.6
  • DOI: DOI:10.1007/s12185-011-0850-7
  • Peer Reviewed
• [Journal Article] Targeting myeloma-osteoclast interaction with V9V2 T cells (2011)
  • Author(s): Qu Cui, Hironobu Shibata, Asuka Oda, Hiroe Amou, Ayako Nakano, Kenichiro Yata, Masahiro Hiasa, Keiichiro Watanabe, Shingen Nakamura, Hirokazu Miki, Takeshi Harada, Shiroh Fujii, Kumiko Kagawa, Kyoko Takeuchi, Shuji Ozaki, Toshio Matsumoto and Masahiro Abe
  • Journal Title: International Journal of Hematology Volume: Vol.94, No.1 Pages: 63-70
  • DOI: DOI:10.1007/s12185-011-0885-9
  • Peer Reviewed
• [Journal Article] The serine/threonine kinase Pim-2 is a novel anti-apoptotic mediator in myeloma cells (2011)
  • Author(s): J Asano, A Nakano, A Oda, H Amou, Masahiro Hiasa, Kyoko Takeuchi, H Miki, S Nakamura, T Harada, Shiroh Fujii, Kumiko Kagawa, Itsuro Endo, Ken-ichiro Yata, A Sakai, Shuji Ozaki, Toshio Matsumoto and Masahiro Abe
  • Journal Title: Leukemia
  • DOI: DOI:10.1038/leu.2011.60
  • Peer Reviewed
• [Presentation] Pim-2 acts as a common downstream mediator to suppress bone formation in myeloma (2012)
  • Author(s): 日浅雅博
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2012-10-20
• [Presentation] RelB attenuates the activation of the classical NF-κB pathway to facilitate osteoblastogenesis (2012)
  • Author(s): Masahiro Hiasa
  • Organizer: ANZBMS 22nd Annual Scientific Meeting
  • Place of Presentation: Pan Pacific Hotel (Australia)
  • Year and Date: 2012-09-05
• [Presentation] A novel role of NF-κB relB in bone remodeling (2011)
  • Author(s): 日浅雅博
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-29
• [Presentation] Prevention of tumor growth and bone destruction in myeloma by Pim kinase inhibition (2011)
  • Author(s): Masahiro Hiasa
  • Organizer: ASBMR 2011 Annual Meeting
  • Place of Presentation: San Diego Convention Center (USA)
  • Year and Date: 2011-09-19
• [Presentation] Pimキナーゼ阻害による腫瘍進展と骨破壊の抑制 (2011)
  • Author(s): 日浅雅博
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2011-09-16
• [Presentation] Dual effects of Pim inhibition on myeloma: induction of bone formation and tumor suppression (2011)
  • Author(s): Masahiro Hiasa
  • Organizer: IOF-ANZBMS 2011 Annual Meeting
  • Place of Presentation: Gold Coast Convention Centre (Australia)
  • Year and Date: 2011-09-06
• [Presentation] Pimキナーゼの阻4害は骨芽細胞分化を促進し、骨髄腫骨病変の形成と腫瘍進展を抑制する (2011)
  • Author(s): 日浅雅博
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2011-07-28