Exosomal S100A9 promotes lung metastasis of adenoid cystic carcinoma via activating cancer-associated fibroblasts

Cancer research · Chronic lymphocytic leukemia

Exosomal S100A9 promotes lung metastasis of adenoid cystic carcinoma via activating cancer‑associated fibroblasts.

Adenoid cystic carcinoma (ACC) is a malignant epithelial neoplasm that arises in secretory glands and commonly metastasizes to the lungs, remaining the primary cause of patient mortality. Here, we observed that S100A9, a calcium-binding protein, was significantly upregulated in highly metastatic ACC cells and markedly enriched in their derived exosomes. Single-cell RNA sequencing was employed to comprehensively map the tumor microenvironment (TME), revealing robust intercellular communication between epithelial cells and cancer-associated fibroblasts (CAFs). Mechanistically, S100A9-enriched exosomes reprogrammed normal fibroblasts, resulting in the acquisition of an activated CAF phenotype characterized by the upregulation of FAP and α‑SMA expression, and enrichment of IL-17, TNF‑α, and NF‑κB signaling pathways. Functionally, these exosome‑educated CAFs promoted the epithelial‑mesenchymal transition in ACC cells and facilitated lung metastasis in vivo via an IL‑17‑dependent signaling axis. Overall, these findings establish exosomal S100A9 as a crucial mediator of TME reprogramming, suggesting that targeting the S100A9‑IL‑17 axis may serve as a promising therapeutic strategy for disrupting ACC lung metastasis.

Because it identifies exosomal S100A9 as a mediator of metastatic progression and a potential therapeutic target.

Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.

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