Emerging Topics on Disseminated Cancer Cell Dormancy and the Paradigm of Metastasis
Emerging Topics on Disseminated Cancer Cell Dormancy and the Paradigm of Metastasis
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DOI：
10.1146/annurev-cancerbio-030617-050446
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发表时间：
2018-01-01
期刊：
影响因子：
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通讯作者：
Sosa, Maria Soledad
中科院分区：
文献类型：
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作者：
Aguirre-Ghiso, Julio A.;Sosa, Maria Soledad
播散性肿瘤细胞(DTC)是公认的转移种子。然而，转移性病变可在原发肿瘤切除数年或数十年后出现症状。这一临床发现表明，树突状细胞不能立即启动生长，可以持续处于休眠状态。在这里，我们回顾了可能导致DTC休眠的三种潜在情景的最新数据：(A)靶器官微环境指示DTC进入休眠；(B)原发肿瘤预先编码休眠信号，只有当DCs进入产生休眠诱导线索的靶器官时才变得明显；以及(C)早期传播产生DTC，由于与正常细胞密切相关，DTC将保持对休眠指示信号的反应能力，并在靶器官进入休眠。文献支持这些情况的存在，并为如何预防转移提供了洞察力。重要的是，在IV期癌症中联合靶向潜伏期和增殖期的DTCs也可能改善这种临床环境下的预后。
Disseminated tumor cells (DTCs) are recognized as the seeds of metastasis. However, metastatic lesions can become symptomatic years or decades after primary tumor removal. This clinical finding suggests that DTCs are not immediately competent to initiate growth and can persist in a dormant state. Here we review recent data for three potential scenarios that could result in DTC dormancy: (a) The target organ microenvironment instructs DTCs to enter dormancy; (b) primary tumors pre encode a dormancy signature that only becomes evident when DTCs enter target organs that produce dormancy inducing cues; and (c) early dissemination spawns DTCs that, by virtue of being closely related to normal cells, would retain the capacity to respond to dormancy instructing signals and enter dormancy in target organs. The literature supports the existence of these scenarios and provides insight into how to prevent metastasis. Importantly, cotargeting dormant and proliferative DTCs in stage IV cancer may also improve outcomes in this clinical setting.