Cancer cells are able to release high amounts of extracellular vesicles, thereby conditioning the normal cells in the surrounding tissue and/or in distant target organs. In the context of bone cancers, previous studies suggested that osteosarcoma cancer cells produce transforming extracellular vesicles able to induce a tumour-like phenotype in normal recipient cells. Indeed, phosphoinositide-specific phospholipase C (PI-PLC) enzymes are differentially expressed in osteosarcoma cell lines with increasing aggressiveness, thus providing helpful insights to better define their role and functions in this bone tumour. By confocal microscopy analysis, we demonstrated that osteosarcoma-derived extracellular vesicles convey all the assessed PI-PLC isoforms, and that they localize into cell membrane bubble-like structures, resembling extracellular vesicles about to be released, as conveyed and/or membrane protein. Cytofluorimetric analysis confirmed the presence of PI-PLC isoforms in the extracellular vesicles collected from conditioned media of osteosarcoma cells. These findings suggest the feasibility to use circulating extracellular vesicles as biomarkers of osteosarcoma progression and/or the monitoring of this distressing disease.

癌细胞能够释放大量的细胞外囊泡，从而调节周围组织和/或远处靶器官中的正常细胞。在骨癌的背景下，先前的研究表明骨肉瘤癌细胞产生能够在正常受体细胞中诱导肿瘤样表型的细胞外囊泡。确实，磷酸肌醇特异性磷脂酶C（PI-PLC）酶在骨肉瘤细胞系中的表达随着侵略性的提高而增加，从而提供了有用的见解，可以更好地确定其在这种骨肿瘤中的作用和功能。通过共聚焦显微镜分析，我们证明骨肉瘤来源的细胞外囊泡可传递所有评估的PI-PLC亚型，并且它们位于细胞膜气泡状结构中，类似于即将被释放的细胞外囊泡和/或膜蛋白。细胞荧光分析证实从骨肉瘤细胞的条件培养基收集的细胞外囊泡中存在PI-PLC同工型。这些发现表明使用循环的细胞外囊泡作为骨肉瘤进展的生物标志物和/或监测这种令人痛苦的疾病的可行性。