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<p>Apart from the classic features, it is almost unknown whether there exist other new pathological features during pre-metastatic niche formation in hepatocellular carcinoma (HCC). Our previous works have highlighted the contribution of increased matrix stiffness to lung pre-metastatic niche formation and metastasis in HCC. However, whether increased matrix stiffness influences glucose metabolism and supply of lung pre-metastatic niche remains largely unclear. Here we uncover the underlying mechanism by which matrix stiffness-tuned exosomal miRNAs as the major contributor modulate glucose enrichment during lung pre-metastatic niche formation through decreasing the glucose uptake and consumption of lung fibroblasts and increasing angiogenesis and vascular permeability. Our findings suggest that glucose enrichment, a new characteristic of the lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs, is essential for the colonization and survival of metastatic tumor cells, as well as subsequent metastatic foci growth.</p>

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A glucose-enriched lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs in hepatocellular carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月18日

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  • Yingying Zhao,
  • Hongmei Yu,
  • Jiajun Li,
  • Jiali Qian,
  • Miao Li,
  • Xi Zhang,
  • Mimi Wang,
  • Yaohui Wang,
  • Yinying Dong,
  • Yang You,
  • Qiwen Zhou,
  • Dongmei Gao,
  • Yan Zhao,
  • Binbin Liu,
  • Rongxin Chen,
  • Zhenggang Ren,
  • Zhiming Wang,
  • Kezhi Zhang,
  • Jiefeng Cui

摘要

Apart from the classic features, it is almost unknown whether there exist other new pathological features during pre-metastatic niche formation in hepatocellular carcinoma (HCC). Our previous works have highlighted the contribution of increased matrix stiffness to lung pre-metastatic niche formation and metastasis in HCC. However, whether increased matrix stiffness influences glucose metabolism and supply of lung pre-metastatic niche remains largely unclear. Here we uncover the underlying mechanism by which matrix stiffness-tuned exosomal miRNAs as the major contributor modulate glucose enrichment during lung pre-metastatic niche formation through decreasing the glucose uptake and consumption of lung fibroblasts and increasing angiogenesis and vascular permeability. Our findings suggest that glucose enrichment, a new characteristic of the lung pre-metastatic niche triggered by matrix stiffness-tuned exosomal miRNAs, is essential for the colonization and survival of metastatic tumor cells, as well as subsequent metastatic foci growth.