Bhatia Ranvir, Chang Joanna, Munoz Jessian L, Walker Nykia D
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Biological Sciences, University of Maryland, Baltimore, MD 21250, USA.
Biomedicines. 2023 Jun 1;11(6):1614. doi: 10.3390/biomedicines11061614.
Tumor-derived exosomes play a multifaceted role in preparing the pre-metastatic niche, promoting cancer dissemination, and regulating cancer cell dormancy. A brief review of three types of cells implicated in metastasis and an overview of other types of extracellular vesicles related to metastasis are described. A central focus of this review is on how exosomes influence cancer progression throughout metastatic disease. Exosomes are crucial mediators of intercellular communication by transferring their cargo to recipient cells, modulating their behavior, and promoting tumor pro-gression. First, their functional role in cancer cell dissemination in the peripheral blood by facilitating the establishment of a pro-angiogenic and pro-inflammatory niche is described during organotro-pism and in lymphatic-mediated metastasis. Second, tumor-derived exosomes can transfer molecular signals that induce cell cycle arrest, dormancy, and survival pathways in disseminated cells, promoting a dormant state are reviewed. Third, several studies highlight exosome involvement in maintaining cellular dormancy in the bone marrow endosteum. Finally, the clinical implications of exosomes as biomarkers or diagnostic tools for cancer progression are also outlined. Understanding the complex interplay between tumor-derived exosomes and the pre-metastatic niche is crucial for developing novel therapeutic strategies to target metastasis and prevent cancer recurrence. To that end, several examples of how exosomes or other nanocarriers are used as a drug delivery system to inhibit cancer metastasis are discussed. Strategies are discussed to alter exosome cargo content for better loading capacity or direct cell targeting by integrins. Further, pre-clinical models or Phase I clinical trials implementing exosomes or other nanocarriers to attack metastatic cancer cells are highlighted.
肿瘤来源的外泌体在准备前转移微环境、促进癌症扩散和调节癌细胞休眠方面发挥着多方面的作用。本文简要回顾了与转移相关的三种细胞类型，并概述了与转移相关的其他类型的细胞外囊泡。本综述的核心重点是外泌体如何在整个转移性疾病过程中影响癌症进展。外泌体是细胞间通讯的关键介质，通过将其货物转移到受体细胞、调节其行为并促进肿瘤进展。首先，描述了它们在器官趋向性和淋巴介导的转移过程中，通过促进促血管生成和促炎微环境的建立，在癌细胞外周血扩散中的功能作用。其次，综述了肿瘤来源的外泌体可以传递分子信号，诱导播散细胞中的细胞周期停滞、休眠和生存途径，促进休眠状态。第三，多项研究强调外泌体参与维持骨髓内膜中的细胞休眠。最后，还概述了外泌体作为癌症进展的生物标志物或诊断工具的临床意义。了解肿瘤来源的外泌体与前转移微环境之间的复杂相互作用对于开发针对转移和预防癌症复发的新型治疗策略至关重要。为此，讨论了几个将外泌体或其他纳米载体用作药物递送系统以抑制癌症转移的例子。讨论了改变外泌体货物含量以提高装载能力或通过整合素进行直接细胞靶向的策略。此外，还强调了实施外泌体或其他纳米载体攻击转移性癌细胞的临床前模型或I期临床试验。
