Abstract
Oral leukoplakia (OLK) is a common oral potentially malignant disorder with a significant risk of transforming into oral squamous cell carcinoma (OSCC), yet the mechanisms remain poorly understood. Here we show that migrasomes, membranous organelles released by migrating cells, are detectable in epithelial cells of OLK and OSCC tissues and are more abundant in OSCC. Using carcinogenesis models, we transform human dysplastic oral keratinocyte (DOK) into oral carcinoma (DOK-TC) cells. Migrasomes derived from DOK-TC cells enhance interactions between DOK-TC cells and macrophages to promote carcinogenesis. Mechanistically, the uptake of prostaglandin E synthase (PTGES)-enriched migrasomes by macrophages increases PTGES expression and prostaglandin E2 secretion, which in turn induces an SPP1+ macrophage phenotype and promotes migration and proliferation. These findings uncover an unexplored migrasome-dependent immunomodulatory mechanism in OLK carcinogenesis and suggest migrasomal PTGES as a promising biomarker for early OSCC detection and a potential therapeutic target.
Data availability
The mass spectrometry data of migrasomes generated in this study have been deposited in the PRIDE database under accession code PXD067282, https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD067282. Three OLK samples are available from GEO under accession code GSE196296, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE196296. Seven HPV-negative OSCC samples (#1, 7, 17, 30, 39, 46, 49) are available from GEO under accession code GSE234933, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE234933. These data are publicly available. All the other data are available within the Article and its Supplementary Information. No custom code was used. Source data are provided with this paper.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (No. 82101023 (XJ Chen), 82470982 (G Zhou)).
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Conceptualization: G Zhou, XJ Chen, and MJ Jiang. Investigation: MJ Jiang and HY Zhou. Supervision: XJ Chen and G Zhou. Writing (original draft): MJ Jiang and HY Zhou. Writing (review and editing): G Zhou, XJ Chen, and YT Bai.
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Jiang, MJ., Zhou, HY., Bai, YT. et al. Migrasome-transported PTGES amplifies the PGE2 cascade in SPP1+ macrophages to drive oral leukoplakia carcinogenesis. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70824-2
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DOI: https://doi.org/10.1038/s41467-026-70824-2
