Hill Richard P, Marie-Egyptienne Delphine T, Hedley David W
Division of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
Semin Radiat Oncol. 2009 Apr;19(2):106-11. doi: 10.1016/j.semradonc.2008.12.002.
The successful growth of a metastasis, by definition, requires the presence of at least 1 cancer stem cell. Metastasis is a complex process, and an important contributor to this process is the influence of the tissue microenvironment, both cell-cell and cell-matrix interactions and the pathophysiologic conditions in tumors, such as hypoxia. A number of studies have suggested that normal stem cells may reside in "niches," where cell-cell and cell-matrix interactions can provide critical signals to support and maintain the undifferentiated phenotype of the stem cells. In this article, the evidence that these niches may be hypoxic is described, and the potential role that hypoxia may play in maintaining the stem cell phenotype in cancers is discussed. Recent work has suggested that there may be a linkage between the stem cell phenotype and that induced by the process of epithelial-mesenchymal transition (EMT). EMT plays an important role in cell movement and organ formation during embryogenesis, and it is currently hypothesized to be a major mechanism by which epithelial cancers may generate cells that can form metastases. Recent evidence suggests that the expression of certain genes involved in EMT is influenced by low oxygen levels, again suggesting a linkage between stem cells and hypoxia. Whether this supposition is correct remains an open question that will only be answered by further experimentation, but the potential role of hypoxia is critical because of its widespread existence in tumors and its known role in resistance to both radiation and drug treatment.
根据定义，转移灶的成功生长至少需要存在1个癌症干细胞。转移是一个复杂的过程，组织微环境的影响是这一过程的重要促成因素，包括细胞间和细胞与基质的相互作用以及肿瘤中的病理生理状况，如缺氧。许多研究表明，正常干细胞可能存在于“生态位”中，在那里细胞间和细胞与基质的相互作用可以提供关键信号来支持和维持干细胞的未分化表型。在本文中，描述了这些生态位可能缺氧的证据，并讨论了缺氧在维持癌症干细胞表型中可能发挥的潜在作用。最近的研究表明，干细胞表型与上皮-间质转化（EMT）过程所诱导的表型之间可能存在联系。EMT在胚胎发育过程中的细胞运动和器官形成中起重要作用，目前推测它是上皮癌产生可形成转移灶细胞的主要机制。最近的证据表明，参与EMT的某些基因的表达受低氧水平影响，这再次表明干细胞与缺氧之间存在联系。这一假设是否正确仍是一个悬而未决的问题，只有通过进一步实验才能回答，但缺氧的潜在作用至关重要，因为它在肿瘤中广泛存在，且在抗辐射和抗药物治疗中发挥着已知作用。
