Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Republic of Korea.
Department of Biomedical Engineering, School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea.
Lab Chip. 2022 Jul 12;22(14):2726-2740. doi: 10.1039/d2lc00364c.
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.
在临床前和临床研究中，已经证明肿瘤教育的血小板在肿瘤发生、癌症发展和转移中起着关键作用。与癌症衍生趋化因子在血小板激活中的作用不同，癌症衍生的细胞外囊泡（EVs）的作用仍然难以捉摸。在这里，我们发现癌症衍生 EVs 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激活，导致血小板在人血管模拟微流控系统上的黏附增加。此外，用人类血浆衍生 EVs 处理的血管上的血小板黏附水平在转移性和非转移性乳腺癌患者之间表现出良好的区分，曲线下面积（AUC）值为 0.88。虽然 EVs 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）。我们相信这些发现阐明了癌症衍生 EVs 与血小板之间相互作用在预转移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。
