文章目录

黑色素瘤来源的细胞外小泡通过ngfr依赖机制诱导淋巴管生成和转移

原文发布日期：2021-11-25

英文摘要：

摘要翻译：

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黑色素瘤来源的细胞外小泡通过ngfr依赖机制诱导淋巴管生成和转移

Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism

原文发布日期：2021-11-25

英文摘要：

Secreted extracellular vesicles (EVs) influence the tumor microenvironment and promote distal metastasis. Here we analyzed the involvement of melanoma-secreted EVs in lymph node pre-metastatic niche formation in murine models. We found that small EVs (sEVs) derived from metastatic melanoma cell lines were enriched in nerve growth factor (NGF) receptor (NGFR, p75NTR), spread through the lymphatic system and were taken up by lymphatic endothelial cells, reinforcing lymph node metastasis. Remarkably, sEVs enhanced lymphangiogenesis and tumor cell adhesion by inducing ERK kinase, nuclear factor (NF)-κB activation and intracellular adhesion molecule (ICAM)-1 expression in lymphatic endothelial cells. Importantly, ablation or inhibition of NGFR in sEVs reversed the lymphangiogenic phenotype, decreased lymph node metastasis and extended survival in pre-clinical models. Furthermore, NGFR expression was augmented in human lymph node metastases relative to that in matched primary tumors, and the frequency of NGFR+ metastatic melanoma cells in lymph nodes correlated with patient survival. In summary, we found that NGFR is secreted in melanoma-derived sEVs, reinforcing lymph node pre-metastatic niche formation and metastasis.

摘要翻译：

表皮生长因子外泌体（EVs）影响肿瘤微环境并促进远处转移。在这里，我们分析了黑色素瘤分泌的外泌体在小鼠模型中对淋巴节点前转移性 niche 形成的作用。我们发现，来源于转移性黑色素瘤细胞系的小外泌体（sEVs）富含神经生长因子受体 (NGFR, p75NTR)，通过淋巴循环转运，并被淋巴血管内皮细胞摄取，从而强化淋巴节点转移。特别值得注意的是，小外泌体通过诱导淋巴管生成和肿瘤细胞附着，上调了淋巴血管内皮细胞中的ERK激酶、NF-κB激活以及内膜分子ICAM-1的表达。重要的是，小外泌体中NGFR的消除或抑制逆转了淋巴管增殖表型，并减少了淋巴节点转移和延长了预临床模型患者的生存期。此外，在人肿瘤转移性淋巴节点中，NGFR的表达比原发肿瘤高，淋巴节点中NGFR+转移性黑色素瘤细胞的比例与患者生存率相关。总之，我们发现 NGFR 被黑色素瘤来源的小外泌体分泌，并强化了淋巴节点前转移性 niche 形成和转移。