Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Department of Clinical Laboratory, The First People's Hospital of Kunshan Affiliated to Jiangsu University, Suzhou, Jiangsu 215300, P.R. China.
Int J Oncol. 2021 Apr;58(4). doi: 10.3892/ijo.2021.5184. Epub 2021 Mar 2.
Tumor metastasis is a destructive characteristic of malignant tumors and the fundamental reason why malignant tumors are difficult to cure. The concept of a pre‑metastatic niche (PMN) provides a novel way to elucidate the molecular mechanism of tumor metastasis. At present, the PMN has been considered as a critical determinant priming distal sites for metastasis. Accumulating evidence has suggested that exosomes are cellular communicators serving a pivotal role in mediating tumor cell metastasis by establishing the PMN. Among exosomal cargos, non‑coding RNAs and proteins are two commonly studied components; however, the latter has received less attention. The present review aimed to summarize the findings regarding cargo proteins selectively loaded in malignant tumor‑derived exosomes. Metastasis‑associated proteins have been demonstrated to be selectively enriched in malignant tumor‑derived exosomes. Exosomal proteins promote PMN formation to mediate the site‑specific metastasis of tumor cells by inducing lymphangiogenesis, angiogenesis and permeability, educating stromal cells, remodeling the extracellular matrix, and suppressing the antitumor immune response. These exosomal proteins have great potential in predicting organ‑directed metastasis and prognosis, as well as in cancer therapy.
肿瘤转移是恶性肿瘤的破坏性特征，也是恶性肿瘤难以治愈的根本原因。前转移灶微环境（PMN）的概念为阐明肿瘤转移的分子机制提供了新的途径。目前，PMN 被认为是启动转移远端部位的关键决定因素。越来越多的证据表明，外泌体作为细胞通讯者，通过建立 PMN 在介导肿瘤细胞转移中发挥关键作用。在外泌体 cargo 中，非编码 RNA 和蛋白质是两个常见的研究成分；然而，后者受到的关注较少。本综述旨在总结关于选择性加载在恶性肿瘤衍生的外泌体中的 cargo 蛋白的研究结果。已经证明，转移相关蛋白在外泌体中被选择性富集。外泌体蛋白通过诱导淋巴管生成、血管生成和通透性、教育基质细胞、重塑细胞外基质以及抑制抗肿瘤免疫反应，促进 PMN 的形成，从而介导肿瘤细胞的特异性转移。这些外泌体蛋白在预测器官定向转移和预后以及癌症治疗方面具有巨大潜力。
