Department of Surgery, McGill University, Montréal, QC H3A 0G4, Canada.
Fondazione Istituto G. Giglio, 90015 Cefalù, Italy.
Cells. 2023 Jun 6;12(12):1566. doi: 10.3390/cells12121566.
Metastases are responsible for the vast majority of cancer deaths, yet most therapeutic efforts have focused on targeting and interrupting tumor growth rather than impairing the metastatic process. Traditionally, cancer metastasis is attributed to the dissemination of neoplastic cells from the primary tumor to distant organs through blood and lymphatic circulation. A thorough understanding of the metastatic process is essential to develop new therapeutic strategies that improve cancer survival. Since Paget's original description of the "Seed and Soil" hypothesis over a hundred years ago, alternative theories and new players have been proposed. In particular, the role of extracellular vesicles (EVs) released by cancer cells and their uptake by neighboring cells or at distinct anatomical sites has been explored. Here, we will outline and discuss these alternative theories and emphasize the horizontal transfer of EV-associated biomolecules as a possibly major event leading to cell transformation and the induction of metastases. We will also highlight the recently discovered intracellular pathway used by EVs to deliver their cargoes into the nucleus of recipient cells, which is a potential target for novel anti-metastatic strategies.
转移是导致绝大多数癌症死亡的原因,但大多数治疗方法都集中在靶向和中断肿瘤生长上,而不是损害转移过程。传统上,癌症转移归因于肿瘤细胞通过血液和淋巴循环从原发性肿瘤扩散到远处器官。为了开发提高癌症存活率的新治疗策略,彻底了解转移过程至关重要。自一百多年前 Paget 最初描述“种子和土壤”假说以来,已经提出了替代理论和新的参与者。特别是,癌细胞释放的细胞外囊泡 (EVs) 及其被邻近细胞或在不同解剖部位摄取的作用已被探索。在这里,我们将概述和讨论这些替代理论,并强调 EV 相关生物分子的水平转移作为导致细胞转化和诱导转移的一个主要事件。我们还将强调最近发现的 EV 用于将其货物递送到受体细胞核内的细胞内途径,这是新的抗转移策略的潜在目标。
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