Sceneay Jaclyn, Smyth Mark J, Möller Andreas
Cancer Genomics and Genetics Laboratory, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Victoria, 3002, Australia.
Cancer Metastasis Rev. 2013 Dec;32(3-4):449-64. doi: 10.1007/s10555-013-9420-1.
It is rapidly becoming evident that the formation of tumor-promoting pre-metastatic niches in secondary organs adds a previously unrecognized degree of complexity to the challenge of curing metastatic disease. Primary tumor cells orchestrate pre-metastatic niche formation through secretion of a variety of cytokines and growth factors that promote mobilization and recruitment of bone marrow-derived cells to future metastatic sites. Hypoxia within the primary tumor, and secretion of specific microvesicles termed exosomes, are emerging as important processes and vehicles for tumor-derived factors to modulate pre-metastatic sites. It has also come to light that reduced immune surveillance is a novel mechanism through which primary tumors create favorable niches in secondary organs. This review provides an overview of our current understanding of underlying mechanisms of pre-metastatic niche formation and highlights the common links as well as discrepancies between independent studies. Furthermore, the possible clinical implications, links to metastatic persistence and dormancy, and novel approaches for treatment of metastatic disease through reversal of pre-metastatic niche formation are identified and explored.
越来越明显的是，在继发器官中形成促肿瘤的前转移生态位，给治愈转移性疾病的挑战增添了前所未有的复杂性。原发性肿瘤细胞通过分泌多种细胞因子和生长因子来协调前转移生态位的形成，这些因子促进骨髓来源的细胞向未来的转移部位动员和募集。原发性肿瘤内的缺氧以及称为外泌体的特定微泡的分泌，正成为肿瘤衍生因子调节前转移部位的重要过程和载体。还发现免疫监视减弱是原发性肿瘤在继发器官中创造有利生态位的一种新机制。本综述概述了我们目前对前转移生态位形成潜在机制的理解，并强调了独立研究之间的共同联系以及差异。此外，还确定并探讨了可能的临床意义、与转移持续性和休眠的联系，以及通过逆转前转移生态位形成来治疗转移性疾病的新方法。
