[P001] Poster

12:10 PM - 1:00 PM JST(3:10 AM - 4:00 AM UTC)

[P01-123] Inflammatory signaling remodels migrasome proteomic cargo through IL-6 amplifier activation

○Ananda Bagus Richky Digdaya Putra¹, Shogo Saito¹, Masayoshi Tanaka¹, Mina Okochi¹ (1. Institute of Science Tokyo (Japan))

Keywords:

Migrasomes,Extracellular vesicles,Inflammation,Proteomic analysis

[Purpose]
Migrasomes are extracellular vesicles generated by migrating cells and are increasingly recognized as mediators of intercellular communication during inflammation. Previous studies have demonstrated that migrasomes participate in the propagation of IL-6 amplifier signaling. However, how inflammatory stimulation alters the composition of the migrasome remains unclear. This study aimed to characterize proteomic changes in migrasomes upon activation of the IL-6 amplifier.

[Method]
Migrasomes were isolated from MDA-MB-231 breast cancer cells under normal, starvation, and cytokine-stimulated conditions. Proteomic profiling was performed by mass spectrometry, followed by differential expression analysis, protein-protein interaction (PPI) network construction, and functional enrichment analysis using the STRING, Reactome, KEGG, and Gene Ontology databases.

[Results]
Comparative proteomic analysis identified 330 upregulated and 149 downregulated proteins in cytokine-stimulated migrasomes compared with starvation controls, over a total of 1984 proteins detected from migrasomes samples. PPI network analysis revealed enrichment of inflammatory signaling components, including the IL-6 pathway kinase JAK1. In addition, vesicle trafficking-associated SNARE proteins, such as syntaxin-3 (STX3) and syntaxin-4 (STX4), were detected within stimulation-enriched modules. Functional enrichment analysis further demonstrated overrepresentation of pathways related to oxidative phosphorylation, endoplasmic reticulum protein processing, and macromolecular complex organization.

[Consideration]
These findings suggest that IL-6 amplifier activation selectively remodels migrasome cargo by incorporating proteins associated with signaling and intracellular trafficking. The enrichment of metabolic and proteostasis-related pathways indicates coordinated cellular adaptation to cytokine stimulation, reflected in the migrasome composition.

[Conclusion]
Inflammatory stimulation alters the proteomic landscape of migrasomes and promotes the incorporation of signaling and trafficking-related proteins, suggesting that cytokine-responsive migrasomes may contribute to the propagation of inflammatory communication within the tumor microenvironment.