抄録
The innate immune response is the first line of defence against microbial infections. In Drosophila, two major pathways of the innate immune system (the Toll- and IMD-mediated pathways) induce the synthesis of antimicrobial peptides (AMPs) within the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells; however, little is known about their anti-tumour effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval haematopoietic organ called the lymph gland (LG). Here, using RNA-seq analysis, 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 significantly 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. We observed that two AMPs, Drosomycin and Defensin,were taken up by circulating haemocyte-like cells, which were associated with the LG regions and showed reduced cell-to-cell adhesion in the mutants. By contrast, the AMP Diptericin was directly localised at the tumour site without intermediating haemocytes. These results suggest that AMPs have a specific cytotoxic effect that enhances apoptosis exclusively in the tumour cells.
| 元の言語 | 英語 |
|---|---|
| 記事番号 | dmm037721 |
| ジャーナル | DMM Disease Models and Mechanisms |
| 巻 | 12 |
| 発行部数 | 6 |
| DOI | |
| 出版物ステータス | 出版済み - 1 1 2019 |
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All Science Journal Classification (ASJC) codes
- Neuroscience (miscellaneous)
- Medicine (miscellaneous)
- Immunology and Microbiology (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
これを引用
Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants. / Araki, Mayo; Kurihara, Massanori; Kinoshita, Suzuko; Awane, Rie; Sato, Tetsuya; Ohkawa, Yasuyuki; Inoue, Yoshihiro H.
：: DMM Disease Models and Mechanisms, 巻 12, 番号 6, dmm037721, 01.01.2019.研究成果: ジャーナルへの寄稿 › 記事
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TY - JOUR
T1 - Anti-tumour effects of antimicrobial peptides, components of the innate immune system, against haematopoietic tumours in Drosophila mxc mutants
AU - Araki, Mayo
AU - Kurihara, Massanori
AU - Kinoshita, Suzuko
AU - Awane, Rie
AU - Sato, Tetsuya
AU - Ohkawa, Yasuyuki
AU - Inoue, Yoshihiro H.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - The innate immune response is the first line of defence against microbial infections. In Drosophila, two major pathways of the innate immune system (the Toll- and IMD-mediated pathways) induce the synthesis of antimicrobial peptides (AMPs) within the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells; however, little is known about their anti-tumour effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval haematopoietic organ called the lymph gland (LG). Here, using RNA-seq analysis, 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 significantly 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. We observed that two AMPs, Drosomycin and Defensin,were taken up by circulating haemocyte-like cells, which were associated with the LG regions and showed reduced cell-to-cell adhesion in the mutants. By contrast, the AMP Diptericin was directly localised at the tumour site without intermediating haemocytes. These results suggest that AMPs have a specific cytotoxic effect that enhances apoptosis exclusively in the tumour cells.
AB - The innate immune response is the first line of defence against microbial infections. In Drosophila, two major pathways of the innate immune system (the Toll- and IMD-mediated pathways) induce the synthesis of antimicrobial peptides (AMPs) within the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells; however, little is known about their anti-tumour effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval haematopoietic organ called the lymph gland (LG). Here, using RNA-seq analysis, 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 significantly 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. We observed that two AMPs, Drosomycin and Defensin,were taken up by circulating haemocyte-like cells, which were associated with the LG regions and showed reduced cell-to-cell adhesion in the mutants. By contrast, the AMP Diptericin was directly localised at the tumour site without intermediating haemocytes. These results suggest that AMPs have a specific cytotoxic effect that enhances apoptosis exclusively in the tumour cells.
UR - http://www.scopus.com/inward/record.url?scp=85068489753&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068489753&partnerID=8YFLogxK
U2 - 10.1242/dmm.037721
DO - 10.1242/dmm.037721
M3 - Article
C2 - 31160313
AN - SCOPUS:85068489753
VL - 12
JO - DMM Disease Models and Mechanisms
JF - DMM Disease Models and Mechanisms
SN - 1754-8403
IS - 6
M1 - dmm037721
ER -