Scholarlink

<p>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.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月27日

查看全文
  • Chu-wen Chen,
  • Shen-rong Zhang,
  • Yu-meng Yan,
  • Kuang-wu Pan,
  • Fa-rong Ou,
  • Kai Su,
  • Bin Cheng

摘要

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.