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Series GSE121551 Query DataSets for GSE121551
Status Public on Jun 12, 2019
Title Anti-tumor effects of antimicrobial peptides, targets of the innate immune system, against hematopoietic tumors in Drosophila mxc mutants
Organism Drosophila melanogaster
Experiment type Expression profiling by high throughput sequencing
Summary The innate immune response is the first line of defence against microbial infections. In Drosophila, two major immune pathways induce the synthesis of antimicrobial peptides (AMPs) in the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells. However, not much is known about their anti-tumour effects. Drosophila mxc(mbn1) mutants exhibit malignant hyperplasia in a larval haematopoietic organ called the lymph gland (LG). Here, using RNA-Seq analysis, we found that many immunoresponsive genes, including AMP genes, were up-regulated in the mutants. Down-regulation of these pathways by either a Toll or an 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 these five AMPs resulted in enhanced apoptosis in the mutant LGs, while no apoptotic signals were detected in the controls. We observed that two AMPs, Drosomycin and Defensin, were taken up by circulating haemocyte-like cells, which were associated with the LG regions showing reduced cell-to-cell adhesion in the mutants. On the other hand, another AMP, Diptericin, was directly localised at the tumour site without intermediating haemocytes. These results indicate that AMPs have a specific cytotoxic effect that enhance apoptosis exclusively in the tumour cells.
 
Overall design mRNA profiles of 3rd instar larvae wild type (Canton S), the lymph gland tumor phenotye (mbn1) and a hypomorphic allele not displaying any tumor phenotype (G43) were generated by deep sequencing using illumina sequencer.
 
Contributor(s) Araki M, Kurihara M, Kinoshita S, Awane R, Sato T, Ohkawa Y, Inoue YH
Citation(s) 31160313
Submission date Oct 22, 2018
Last update date Jul 09, 2019
Contact name Tetsuya Sato
E-mail(s) sato@bioreg.kyushu-u.ac.jp
Organization name Kyushu University
Street address 3-1-1, Maidashi Higashi-ku
City Fukuoka
ZIP/Postal code 812-8582
Country Japan
 
Platforms (1)
GPL15334 Illumina HiSeq 1000 (Drosophila melanogaster)
Samples (3)
GSM3439145 CantonS
GSM3439146 G43
GSM3439147 mbn1
Relations
BioProject PRJNA497783
SRA SRP166265

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE121551_genes.fpkm_tracking.txt.gz 548.7 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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