Genetic studies on tumor suppression by innate immune system in Drosophila

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06277
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 45010:Genetics-related
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: INOUE Yoshihiro 京都工芸繊維大学, 応用生物学系, 教授 (90201938)
• Co-Investigator(Kenkyū-buntansha): 松田 修 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00271164)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ショウジョウバエ / 造血組織腫瘍 / 自然免疫 / 抗癌ペプチド / 血球細胞

Outline of Final Research Achievements

All but a few higher vertebrates have only an innate immune system, but cancer cells are recognized and eliminated. Drosophila mxc mutants exhibit a leukemia-like phenotype in which undifferentiated cells within hematopoietic tissues proliferate abnormally and infiltrate other tissues. In the presence of a tumor, reactive oxygen species are produced in the hematopoietic cells and recruited to the fat body. There, the innate immune pathway is activated, and families of proteins called AMP or Turandot are produced and secreted. These proteins are taken up by blood cells and transported to the tumor, where apoptosis is induced. Homologous proteins have also been shown to have anti-tumor activity in mice. The innate immune system can recognize and eliminate cancer cells, and these proteins could be new anti-cancer drugs. These proteins have the potential to be new anti-cancer agents.

Free Research Field

発生遺伝学

Academic Significance and Societal Importance of the Research Achievements

ショウジョウバエを用いた癌研究は固形癌を対象としてきたが、本研究では血液腫瘍 (独自に確立)を扱った。mxc変異体の癌細胞が浸潤能を有する白血病モデルになることを証明した。さらに癌の情報が血球細胞を介して脂肪体に伝達され、そこで２つの自然免疫系が活性化される機構を明らかにした。標的である７種類のAMPと２種類のTurandotに抗腫瘍効果があることを示した。それらはいずれも血球細胞に取り込まれ、癌組織にのみアポトーシスを誘導した。この分野の発展にインパクトを与えた。さらにマウスのAMPにも抗腫瘍効果があるとの結果も得られ、副作用のない、新たな抗癌剤となる可能性がある。社会的意義も少なくない。