In preclinical and clinical studies, it has been demonstrated that tumor-educated platelets play a critical role in tumorigenesis, cancer development, and metastasis. Unlike the role of cancer-derived chemokines in platelet activation, the role of cancer-derived extracellular vesicles (EVs) has remained elusive. Here, we found that interleukin-8 (IL-8) in cancer-derived EVs contributed to platelet activation by increasing P-selectin expression and ligand affinity, resulting in increased platelet adhesion on the human vessel-mimicking microfluidic system. Furthermore, platelet adhesion levels on vessels treated with human plasma-derived EVs demonstrated good discrimination between breast cancer patients with metastasis and those without, with the area under the curve (AUC) value of 0.88. While EpCAM expression on EVs could detect the existence of a tumor (AUC = 0.89), it performed poorly in predicting metastasis (AUC = 0.42). We believe that these findings shed light on the role of the interaction between cancer-derived EVs and platelets in pre-metastatic niche formation and tumor metastasis, potentially leading to the development of platelet–tumor interaction-based novel diagnostic and therapeutic strategies.

中文翻译：

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通过细胞外囊泡处理的血小板粘附在血管芯片上预测肿瘤转移

在临床前和临床研究中，已经证明肿瘤诱导的血小板在肿瘤发生、癌症发展和转移中起关键作用。与癌症衍生的趋化因子在血小板活化中的作用不同，癌症衍生的细胞外囊泡 (EV) 的作用仍然难以捉摸。在这里，我们发现癌症衍生 EV 中的白细胞介素 8 (IL-8) 通过增加 P-选择素表达和配体亲和力来促进血小板活化，从而增加血小板在模拟人体血管的微流体系统上的粘附性。此外，用人血浆衍生的 EVs 治疗的血管上的血小板粘附水平证明了转移和未转移的乳腺癌患者之间的良好区分，曲线下面积 (AUC) 值为 0.88。虽然 EV 上的 EpCAM 表达可以检测到肿瘤的存在（AUC = 0.89），但它在预测转移方面表现不佳（AUC = 0.42）。我们相信这些发现揭示了癌症衍生的 EVs 和血小板之间的相互作用在转移前生态位形成和肿瘤转移中的作用，可能导致基于血小板-肿瘤相互作用的新型诊断和治疗策略的发展。