UM is an aggressive intraocular tumor characterized by high plasticity and a propensity to metastasize in the liver. However, the underlying mechanisms governing liver tropism remain poorly understood. Given the emerging significance of exosomes, we sought to investigate the contribution of UM-derived exosomes to specific steps of the metastatic process. Firstly, we isolated exosomes from UM cells sharing a common genetic background and different metastatic properties. A comparison of protein cargo reveals an overrepresentation of proteins related to cytoskeleton remodeling and actin filament-based movement in exosomes derived from the parental cells that may favor the detachment of cells from the primary site. Secondly, we assessed the role of macrophages in reprogramming the HHSCs by exosomes. The activation of HHSCs triggered a pro-inflammatory and pro-fibrotic environment through cytokine production, upregulation of extracellular matrix molecules, and the activation of signaling pathways. Finally, we found that activated HHSCs promote increased adhesion and migration of UM cells. Our findings shed light on the pivotal role of exosomes in pre-metastatic niche construction in the liver.
葡萄膜黑色素瘤是一种具有高度可塑性和肝脏转移倾向的侵袭性眼内肿瘤。然而，其肝脏趋向性的潜在机制尚不明确。鉴于外泌体日益凸显的重要性，本研究旨在探讨葡萄膜黑色素瘤来源外泌体在转移过程中的具体作用机制。首先，我们从具有相同遗传背景但不同转移特性的葡萄膜黑色素瘤细胞中分离出外泌体。通过蛋白质组学比较发现，亲代细胞来源的外泌体中富含与细胞骨架重塑和肌动蛋白丝运动相关的蛋白质，这可能促进肿瘤细胞从原发灶脱离。其次，我们评估了巨噬细胞通过外泌体重编程肝星状细胞的作用。激活的肝星状细胞通过细胞因子分泌、细胞外基质分子上调和信号通路激活，引发了促炎和促纤维化的微环境。最后，我们发现活化的肝星状细胞能够促进葡萄膜黑色素瘤细胞的黏附和迁移能力增强。本研究揭示了外泌体在肝脏转移前微环境形成中的关键作用。
肿瘤(癌症)患者之家