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<p>Cancer stem cells (CSC) play a crucial role in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutic resistance. However, the underlying mechanisms and potential targeted treatment strategies remain poorly understood. In this study, we employed single-cell RNA sequencing and exosomal profiling, identifying TSPAN8-enriched exosomes secreted by CSC, which are associated with poor survival rates in PDAC patients. They enhanced stemness in the surrounding non-stem cancer cells (NSCC) by activating the Sonic Hedgehog (Hh) signalling pathway. This exosomal TSPAN8-Hh signalling axis significantly increases the clonogenic ability, invasiveness, and chemoresistance of PDAC cells. Furthermore, TSPAN8-enriched exosomes promoted a higher stem cell frequency, tumourigenicity, and tumour growth rate in vivo, confirming their critical roles in PDAC malignant progression. Our findings underscore the importance of TSPAN8-enriched exosomes for CSC-NSCC communication during PDAC progression.</p>

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Cancer stem cells-derived exosomal TSPAN8 enhances non-stem cancer cells stemness and promotes malignant progression in PDAC

  • 期刊论文

  • 发表日期：

    2025年4月18日

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  • Xiaoyi Yang,
  • Rujiao Liu,
  • Juan Jin,
  • Jingxuan Xv,
  • Jiahao Wu,
  • Yijie Jin,
  • Yaya Zhang,
  • Shan Chen,
  • Bin Sun,
  • Mou-bin Lin,
  • Wumaier Reziya,
  • Junjian Li,
  • Haoyu Sun,
  • Hongxia Wang,
  • Bo Yu,
  • Guangjian Fan,
  • Wenting Liu

摘要

Cancer stem cells (CSC) play a crucial role in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutic resistance. However, the underlying mechanisms and potential targeted treatment strategies remain poorly understood. In this study, we employed single-cell RNA sequencing and exosomal profiling, identifying TSPAN8-enriched exosomes secreted by CSC, which are associated with poor survival rates in PDAC patients. They enhanced stemness in the surrounding non-stem cancer cells (NSCC) by activating the Sonic Hedgehog (Hh) signalling pathway. This exosomal TSPAN8-Hh signalling axis significantly increases the clonogenic ability, invasiveness, and chemoresistance of PDAC cells. Furthermore, TSPAN8-enriched exosomes promoted a higher stem cell frequency, tumourigenicity, and tumour growth rate in vivo, confirming their critical roles in PDAC malignant progression. Our findings underscore the importance of TSPAN8-enriched exosomes for CSC-NSCC communication during PDAC progression.