Hood Joshua L, Pan Hua, Lanza Gregory M, Wickline Samuel A
Division of Cardiology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63108, USA.
Lab Invest. 2009 Nov;89(11):1317-28. doi: 10.1038/labinvest.2009.94. Epub 2009 Sep 28.
Cancers use a nanoscale messenger system known as exosomes to communicate with surrounding tissues and immune cells. However, the functional relationship between tumor exosomes, endothelial signaling, angiogenesis, and metastasis is poorly understood. Herein, we describe a standardized approach for defining the angiogenic potential of isolated exosomes. We created a powerful technique to rapidly and efficiently isolate and track exosomes for study using dynamic light scattering in conjunction with fluorescent exosome labeling. With these methods, melanoma exosomes were observed to interact with and influence endothelial tubule morphology as well as move between endothelial tubule cells by means of tunneling nanotube structures. Melanoma exosomes also were observed to rapidly stimulate the production of endothelial spheroids and endothelial sprouts in a dose-dependent manner. In concert, tumor exosomes simultaneously elicited paracrine endothelial signaling by regulation of certain inflammatory cytokines. These data suggest that, tumor exosomes can promote endothelial angiogenic responses, which could contribute to tumor metastatic potential.
癌症利用一种称为外泌体的纳米级信使系统与周围组织和免疫细胞进行通信。然而，肿瘤外泌体、内皮信号传导、血管生成和转移之间的功能关系仍知之甚少。在此，我们描述了一种用于定义分离的外泌体血管生成潜力的标准化方法。我们创建了一种强大的技术，通过结合动态光散射和荧光外泌体标记，快速有效地分离和追踪外泌体用于研究。通过这些方法，观察到黑色素瘤外泌体与内皮小管形态相互作用并影响其形态，还通过隧道纳米管结构在内皮小管细胞之间移动。还观察到黑色素瘤外泌体以剂量依赖的方式迅速刺激内皮球体和内皮芽的产生。同时，肿瘤外泌体通过调节某些炎性细胞因子同时引发旁分泌内皮信号传导。这些数据表明，肿瘤外泌体可促进内皮血管生成反应，这可能有助于肿瘤转移潜力。
