Multiple Myeloma (MM) is an incurable haematological malignancy caused by uncontrolled growth of plasma cells. MM pathogenesis is attributed to crosstalk between plasma cells and the bone marrow microenvironment, where extracellular vesicles (EVs) play a role. In this study, EVs secreted from a panel of MM cell lines were isolated from conditioned media by ultracentrifugation and fluorescently stained EVs were co-cultured with THP-1 monocyte cells. MM EVs from three cell lines displayed a differential yet dose-dependent uptake by THP-1 cells, with H929 EVs displaying the greatest EV uptake compared to MM.1s and U266 EVs suggesting that uptake efficiency is dependent on the cell line of origin. Furthermore, MM EVs increased the secretion of MMP-9 and IL-6 from monocytes, with H929 EVs inducing the greatest effect, consistent with the greatest uptake efficiency. Moreover, monocyte-conditioned media collected following H929 EV uptake significantly increased the migration and proliferation of MM cells. Finally, EV proteome analysis revealed differential cargo enrichment that correlates with disease progression including a significant enrichment of spliceosome-related proteins in H929 EVs compared to the U266 and MM.1s EVs. Overall, this study demonstrates that MM-derived EVs modulate monocyte function to promote tumour growth and metastasis and reveals possible molecular mechanisms involved.
多发性骨髓瘤（MM）是一种由浆细胞不受控增殖导致的不可治愈的血液系统恶性肿瘤。其发病机制与浆细胞和骨髓微环境之间的相互作用密切相关，而细胞外囊泡（EVs）在这一过程中发挥重要作用。本研究通过超速离心法从多发性骨髓瘤细胞系的条件培养基中分离出分泌的EVs，并将荧光标记的EVs与THP-1单核细胞共培养。结果显示，三种MM细胞系来源的EVs在THP-1细胞中呈现差异性的剂量依赖性摄取，其中H929来源的EVs摄取效率显著高于MM.1s和U266来源的EVs，表明摄取效率取决于来源细胞系。此外，MM EVs能促进单核细胞分泌MMP-9和IL-6，且H929 EVs诱导作用最强，与其最高摄取效率一致。进一步研究发现，经H929 EVs处理后的单核细胞条件培养基能显著增强MM细胞的迁移和增殖能力。最后，EV蛋白质组学分析显示不同细胞系来源的EVs携带差异性的功能分子，其中H929 EVs中剪接体相关蛋白的富集程度显著高于U266和MM.1s EVs，这与疾病进展相关。综上所述，本研究证实MM来源的EVs通过调控单核细胞功能促进肿瘤生长和转移，并揭示了其中可能涉及的分子机制。
肿瘤(癌症)患者之家