2020 Fiscal Year Final Research Report
Genetic studies on tumor suppression by innate immune system in Drosophila
| Project/Area Number |
17K07500
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Genetics/Chromosome dynamics
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| Research Institution | Kyoto Institute of Technology |
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Principal Investigator |
Inoue Yoshihiro 京都工芸繊維大学, 応用生物学系, 教授 (90201938)
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| Co-Investigator(Kenkyū-buntansha) |
山口 政光 京都工芸繊維大学, 応用生物学系, 教授 (00182460)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Keywords | anti-microbial peptide / Drosophila / 造血器腫瘍 / RNA-sequencing |
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| Outline of Final Research Achievements |
In Drosophila, two major pathways of the innate immune system induce the synthesis of AMPs within the fat body. Drosophila mxc mutants exhibit malignant hyperplasia in a larval haematopoietic organ called the lymph gland. We found many immunoresponsive genes, including those encoding AMPs, to be upregulated in these mutants. Downregulation of these pathways by either a Toll or imd mutation enhanced the tumour phenotype of the mxc mutants. Conversely, ectopic expression of each of five different AMPs in the fat body suppressed the LG hyperplasia phenotype in the mutants. Thus, we propose that the Drosophila innate immune system can suppress the progression of haematopoietic tumours by inducing AMP gene expression. Overexpression of any one of the five AMPs studied resulted in enhanced apoptosis in mutant LGs, whereas no apoptotic signals were detected in controls. These results suggest that AMPs have a specific cytotoxic effect that enhances apoptosis exclusively in the tumour cells.
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| Free Research Field |
発生遺伝学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、獲得免疫系を持たないショウジョウバエでも、自己の細胞に由来する癌細胞に応答して、自然免疫系を活性化できること、その結果、AMPが誘導され、体液中に分泌さえること、AMPの種類により直接癌細胞上に作用したり、体液中の血球細胞にAMPが取り込まれて、癌細胞に作用することがわかった。一方、正常組織にはAMPは作用しない。AMPが癌細胞だけに作用するメカニズムは不明であるが、ショウジョウバエの血球細胞は脊椎動物のマクロファージに相当する。それが癌細胞と正常細胞の認識を行なっている可能性は高い。自然免疫系により誘導されるAMPは副作用のない抗がん剤になる可能性がある。
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