从葡萄膜黑色素瘤（UM）细胞分泌的胞外囊泡参与了前转移基质的建立，并表现出促进转移的潜力，特别是在肝脏中。在本研究中，我们在体外培养了人类原发性UM细胞和葡萄膜黑色素瘤相关的成纤维细胞，通过感染携带自杀基因融合酵母胞嘧啶脱氨酶::尿嘧啶磷酸核糖转移酶（yCD::UPRT）的逆转录病毒，使其转导。整合了前病毒的yCD::UPRT-UM细胞群体表达了该基因，并持续分泌着携带自杀基因mRNA的小型胞外囊泡（sEVs）。 yCD::UPRT-UM-sEVs被肿瘤细胞内化，以将前药5-氟脱氨胞苷（5-FC）转化为细胞毒性药物5-氟尿嘧啶（5-FU）。 yCD::UPRT-UM-sEVs的宿主范围不仅限于UM。在体外， yCD::UPRT-UM-sEVs在不同程度上抑制了人类皮肤黑素瘤细胞系A375和葡萄膜黑色素瘤细胞系MP38以及其他原发性UM的生长。 yCD::UPRT-UM-sEVs具有成为UM的治疗和预防潜力的可能性。然而，使用yCD::UPRT-UM-sEVs必须首先在动物临床前研究中进行测试。

Extracellular vesicles secreted from uveal melanoma (UM) cells are involved in the establishment of the premetastatic niche and display transforming potential for the formation of metastases, preferentially in the liver. In this study, we cultivated human primary UM cells and uveal melanoma-associated fibroblasts in vitro to be transduced by infection with a retrovirus containing the suicide gene-fused yeast cytosine deaminase::uracil phospho-ribosyl transferase (yCD::UPRT). A homogenous population of yCD::UPRT-UM cells with the integrated provirus expressed the gene, and we found it to continuously secrete small extracellular vesicles (sEVs) possessing mRNA of the suicide gene. The yCD::UPRT-UM-sEVs were internalized by tumor cells to the intracellular conversion of the prodrug 5-fluorocytosine (5-FC) to the cytotoxic drug 5-fluorouracil (5-FU). The host range of the yCD::UPRT-UM-sEVs was not limited to UMs only. The yCD::UPRT-UM-sEVs inhibited the growth of the human cutaneous melanoma cell line A375 and uveal melanoma cell line MP38, as well as other primary UMs, to various extents in vitro. The yCD::UPRT-UM-sEVs hold the therapeutic and prophylactic potential to become a therapeutic drug for UM. However, the use of yCD::UPRT-UM-sEVs must first be tested in animal preclinical studies.