Drosophila hemocytes recognize lymph gland tumors of mxc mutants and activate the innate immune pathway in a reactive oxygen species-dependent manner.
Drosophila
Dual oxidase
Hemocytes
Innate immunity
ROS
Tumor
Journal
Biology open
ISSN: 2046-6390
Titre abrégé: Biol Open
Pays: England
ID NLM: 101578018
Informations de publication
Date de publication:
01 11 2022
01 11 2022
Historique:
received:
07
07
2022
accepted:
03
10
2022
pubmed:
14
10
2022
medline:
5
11
2022
entrez:
13
10
2022
Statut:
ppublish
Résumé
Mechanisms of cancer cell recognition and elimination by the innate immune system remains unclear. The immune signaling pathways are activated in the fat body to suppress the tumor growth in mxcmbn1 hematopoietic tumor mutants in Drosophila by inducing antimicrobial peptides (AMP). Here, we investigated the regulatory mechanism underlying the activation in the mutant. Firstly, we found that reactive oxygen species (ROS) accumulated in the hemocytes due to induction of dual oxidase and one of its activators. This was required for the AMP induction and the tumor growth suppression. Next, more hemocytes transplanted from normal larvae were associated with the mutant tumor than normal lymph glands (LGs). Matrix metalloproteinase 1 and 2 (MMP2) were highly expressed in the tumors. The basement membrane components in the tumors were reduced and ultimately lost inside. Depletion of the MMP2 rather than MMP1 resulted in a significantly reduced AMP expression in the mutant larvae. The hemocytes may recognize the disassembly of basement membrane in the tumors and activate the ROS production. Our findings highlight the mechanism via which macrophage-like hemocytes recognize tumor cells and subsequently convey the information to induce AMPs in the fat body. They contribute to uncover the role of innate immune system against cancer.
Identifiants
pubmed: 36226812
pii: 277211
doi: 10.1242/bio.059523
pmc: PMC9641529
pii:
doi:
Substances chimiques
Drosophila Proteins
0
Matrix Metalloproteinase 2
EC 3.4.24.24
Mxc protein, Drosophila
0
Reactive Oxygen Species
0
Tumor Suppressor Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : JSPS
ID : 17K07500
Organisme : Kyoto Institute of Technology
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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