The communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high-metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin-NF-κB signaling in fibroblasts. Activated CAFs further promote cancer progression by secreting pro-inflammatory cytokines, including IL-6 and IL-8. Clinical data show high serum exosomal miR-1247-3p levels correlate with lung metastasis in HCC patients. These results demonstrate intercellular crosstalk between tumor cells and fibroblasts is mediated by tumor-derived exosomes that control lung metastasis of HCC, providing potential targets for prevention and treatment of cancer metastasis.

中文翻译：

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肿瘤来源的外泌体miR-1247-3p诱导与癌症相关的成纤维细胞活化，从而促进肝癌的肺转移。

转移利基中肿瘤来源的元素与基质之间的通讯在促进癌症转移中起着至关重要的作用。然而，尚未完全了解肿瘤细胞用于控制转移性小生境形成的机制。在这里，我们报告说，在肺转移小生境中，高转移性肝细胞癌（HCC）细胞比低转移性HCC细胞具有更大的能力将正常成纤维细胞转化为癌症相关的成纤维细胞（CAF）。我们显示高转移性HCC细胞分泌直接靶向B4GALT3的外泌体miR-1247-3p，从而导致成纤维细胞激活β1-整合素-NF-κB信号。活化的CAF通过分泌促炎性细胞因子（包括IL-6和IL-8）进一步促进癌症进展。临床数据显示，高血清外泌体miR-1247-3p水平与HCC患者的肺转移有关。