Extracellular Vesicles Arising from Apoptotic Cells in Tumors: Roles in Cancer Pathogenesis and Potential Clinical Applications.
Extracellular Vesicles Arising from Apoptotic Cells in Tumors: Roles in Cancer Pathogenesis and Potential Clinical Applications.
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DOI：
10.3389/fimmu.2017.01174
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发表时间：
2017
影响因子：
7.3
通讯作者：
Gregory CD
中科院分区：
文献类型：
--
作者：
Lynch C;Panagopoulou M;Gregory CD
已知凋亡细胞对肿瘤微环境的影响是多种多样的。越来越多的证据表明，尽管细胞凋亡在肿瘤抑制中发挥着众所周知的作用，但它也可能通过多种机制促进癌性进化或治疗后复发。这些包括免疫调节、抗炎和细胞凋亡的营养环境反应，它们驱动肿瘤进展。我们的团队引入了术语“肿瘤再生生态位（ORN）”来描述在癌症中被劫持的保守细胞死亡驱动的组织修复和再生机制的概念网络。我们认为，ORN的关键要素之一是细胞外囊泡（EVs），特别是来自凋亡的肿瘤细胞的细胞外囊泡。电动汽车是膜分隔的亚细胞颗粒，其中包含多种生物活性分子，包括其来源的细胞标记物。作为局部和全身细胞间通讯的介质，ev与越来越多的生理和病理背景有关，检测特异性ev可能有助于监测疾病进展。在这里，我们讨论了由凋亡的肿瘤细胞产生的ev的机制——包括组成性的和作为治疗的结果——可能介导宿主对癌症细胞死亡的反应。我们还考虑了如何监测这些电动汽车及其货物在未来可能有助于改善癌症的诊断、分期和治疗效果。
It is known that apoptotic cells can have diverse effects on the tumor microenvironment. Emerging evidence indicates that, despite its renowned role in tumor suppression, apoptosis may also promote oncogenic evolution or posttherapeutic relapse through multiple mechanisms. These include immunomodulatory, anti-inflammatory, and trophic environmental responses to apoptosis, which drive tumor progression. Our group has introduced the term “onco-regenerative niche (ORN)” to describe a conceptual network of conserved cell death-driven tissue repair and regeneration mechanisms that are hijacked in cancer. We propose that, among the key elements of the ORN are extracellular vesicles (EVs), notably those derived from apoptotic tumor cells. EVs are membrane-delimited subcellular particles, which contain multiple classes of bioactive molecules including markers of the cell from which they are derived. EVs are implicated in an increasing number of physiological and pathological contexts as mediators of local and systemic intercellular communication and detection of specific EVs may be useful in monitoring disease progression. Here, we discuss the mechanisms by which EVs produced by apoptotic tumor cells—both constitutively and as a consequence of therapy—may mediate host responsiveness to cell death in cancer. We also consider how the monitoring of such EVs and their cargoes may in the future help to improve cancer diagnosis, staging, and therapeutic efficacy.