Regulation of Tumor associated macrophage number by transcription factor MafB

• Project/Area Number: 16K18398
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: University of Tsukuba
• Principal Investigator: Hamada Michito 筑波大学, 医学医療系, 助教 (20567630)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: MafB / 腫瘍随伴マクロファージ / 転写因子 / 悪性腫瘍 / マクロファージ / 脾臓 / 腫瘍 / TAM / macrophage

Outline of Final Research Achievements

Tumor-associated macrophages (TAMs) have the ability to promote tumor growth by expressing growth factors, angiogenic factors, immunosuppressive factors. In this study, we elucidated the new function of transcription factor MafB and aim to develop new cancer therapeutics targeting macrophages in spleen. Subcutaneous transplantation of mouse lung cancer cells into a mouse (Mafb CKO) deficient in Mafb specifically for macrophages has shown that the size of the tumor is significantly increased. Moreover, in the tumor of Mafb CKO macrophage were increased. This indicates that MafB is a factor that determines the number of macrophages in a tumor.

Academic Significance and Societal Importance of the Research Achievements

MafBを欠損した脾臓マクロファージは、IL-6の発現が亢進し、脾臓のHSCやマクロファージ前駆体のM-CSFの取り込みを促進させてしまうことによって、TAM数を増加させ、腫瘍成長を促進することが明らかとなった。この機構は、脾臓におけるTAMの産生メカニズムを明らかにした新しい発見であり、さらなる詳細な解析によって今後の新たながん治療の基盤確立にも繋がると考える。

Research Products

• [Journal Article] Mice harboring an MCTO mutation exhibit renal failure resembling nephropathy in human patients (2019)
  • Author(s): Yuki TSUNAKAWA, Michito HAMADA, Yurina MATSUNAGA, Sayaka FUSEYA, Hyojung JEON, Yuji WAKIMOTO, Toshiaki USUI, Maho KANAI, Seiya MIZUNO, Naoki MORITO, Satoru TAKAHASHI
  • Journal Title: Experimental Animals Volume: 68 Issue: 1 Pages: 103-111
  • DOI: 10.1538/expanim.18-0093
  • NAID: 130007604455
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed
• [Journal Article] MafB is a critical regulator of complement component C1q (2017)
  • Author(s): Tran, M.T.N., Hamada, M., Jeon, H.J., Shiraishi, R., Asano, K., Hattori, M., Nakamura, M., Imamura, Y., Tsunakawa, Y., Fujii, R., Kulathunga, K., Andrea, C.S., Koshida, R., Kamei, R., Matsunaga, Y., Kobayashi, M., Oishi, H., Kudo, T. and Takahashi, S.
  • Journal Title: Nature Commun. Volume: 8 Issue: 1 Pages: 1700-1700
  • DOI: 10.1038/s41467-017-01711-0
  • NAID: 120007128749
  • Peer Reviewed / Open Access
• [Presentation] 転写因子MafBのマクロファージにおける機能解析 (2018)
  • Author(s): 濱田理人
  • Organizer: 第65回日本実験動物学会
  • Invited
• [Presentation] Homeostatic function of MafB in macrophages (2018)
  • Author(s): 濱田理人
  • Organizer: 47th annual scientific meeting International society for experimental hematology
  • Int'l Joint Research
• [Presentation] The transcription factor MafB is critical regulator of complement component C1q (2018)
  • Author(s): 濱田理人
  • Organizer: The 17th International Joint Mini-Symposium on Molecular and Cell Biology among KU-NTU-UT
  • Int'l Joint Research / Invited
• [Presentation] 創傷治癒における転写因子MafBの機能解析 (2018)
  • Author(s): 井上由理、綱川祐貴、濱田理人、高橋智
  • Organizer: 第41回日本分子生物学会
• [Presentation] 創傷治癒における転写因子MafBの機能解析 (2018)
  • Author(s): 井上由理、綱川祐貴、濱田理人、高橋智
  • Organizer: 第７回 筑波大-理科大合同リトリート
• [Presentation] MafB inhibits tumor growth through regulating the population of Tumor-associated macrophages (2017)
  • Author(s): 今村優希
  • Organizer: 15th international congress on Targeted anticancer therapies
  • Place of Presentation: Marriott Rive Gauche Hotel and Conference Center, France
  • Year and Date: 2017-03-05
  • Int'l Joint Research
• [Presentation] MafB は腫瘍随伴マクロファージを抑制し腫瘍増殖を制御する (2017)
  • Author(s): 井上由理
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] MafB は脾臓における腫瘍随伴マクロファージ前駆体を制御し、がんを抑制する (2017)
  • Author(s): 藤井梨沙
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] MafBは腫瘍随伴マクロファージ数を制御し、がんを抑制する (2017)
  • Author(s): 藤井梨紗
  • Organizer: 第5回筑波大学東京理科大学合同リトリート
  • Place of Presentation: 東京理科大学 野田キャンパス （千葉県野田市）
• [Presentation] MafB inhibits tumor growth through regulating the population of Tumor-associated macrophages in the spleen (2016)
  • Author(s): 今村優希
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター (沖縄県宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] MafBは腫瘍随伴マクロファージ数を制御し、がんを抑制する (2016)
  • Author(s): 藤井梨紗
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜 （神奈川県横浜市)
  • Year and Date: 2016-11-30
• [Presentation] The role of MafB in Tumor-associated macrophages and tumor growth (2016)
  • Author(s): 今村優希
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市)
  • Year and Date: 2016-11-30
• [Presentation] The role of MafB in tumor growth. (2016)
  • Author(s): 藤井梨紗
  • Organizer: Tsukuba Global Science week 2016
  • Place of Presentation: つくば国際会議場 (茨城県つくば市）
  • Year and Date: 2016-09-17
  • Int'l Joint Research
• [Presentation] MafB inhibits tumor growth through regulating the population of Tumor-associated macrophages in the spleen (2016)
  • Author(s): 今村優希
  • Organizer: Tsukuba Global Science week 2016
  • Place of Presentation: つくば国際会議場(茨城県つくば市）
  • Year and Date: 2016-09-17
  • Int'l Joint Research
• [Presentation] Transcription factor MafB is indispensable for homeostatic function of macrophages (2016)
  • Author(s): 濱田理人
  • Organizer: 第24回マクロファージ分子細胞生物学国際シンポジウム（MMCB2016）
  • Place of Presentation: sola city Conference Center, （東京都千代田区）
  • Year and Date: 2016-06-04
  • Int'l Joint Research / Invited
• [Remarks] からだの死細胞を取り除く仕組みの解明
  • URL: http://www.tsukuba.ac.jp/attention-research/p201711221900.html