Aggressiveness Niche: Can It Be the Foster Ground for Cancer Metastasis Precursors?
Aggressiveness Niche: Can It Be the Foster Ground for Cancer Metastasis Precursors?
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DOI：
10.1155/2016/4829106
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发表时间：
2016
影响因子：
4.3
通讯作者：
Said N
中科院分区：
文献类型：
--
作者：
ElShamy WM;Sinha A;Said N
肿瘤起始和肿瘤进展之间的关系可以遵循线性投影，其中所有肿瘤细胞被同等地赋予进展为转移的能力。或者，并非所有肿瘤细胞在遗传和/或表观遗传上都是相同的，并且只有少数细胞被诱导成为转移性肿瘤细胞。这些细胞在肿瘤中的位置也会影响这些细胞的命运。肿瘤的最内核，其中形成不利条件的升高的压力，例如坏死诱导的炎症和缺氧诱导的免疫抑制环境，似乎是产生具有转移潜力的这种肿瘤细胞的最肥沃的土壤。在这里，我们将这个坏死/缺氧的核心称为“侵袭性小生境”，并将提供数据来支持其参与产生这些转移性前体。在这个生态位内，缺氧存活细胞与受新招募的间充质基质细胞（MSC），肿瘤相关巨噬细胞（TAM）和其他类型细胞影响的炎症微环境的相互作用以及它们之间双向相互作用的建立提高了这些肿瘤细胞的侵袭性。此外，在这些细胞中诱导的免疫逃避特性很可能有助于形成和维持这种攻击性小生境。
The relationship between tumor initiation and tumor progression can follow a linear projection in which all tumor cells are equally endowed with the ability to progress into metastasis. Alternatively, not all tumor cells are equal genetically and/or epigenetically, and only few cells are induced to become metastatic tumor cells. The location of these cells within the tumor can also impact the fate of these cells. The most inner core of a tumor where an elevated pressure of adverse conditions forms, such as necrosis-induced inflammation and hypoxia-induced immunosuppressive environment, seems to be the most fertile ground to generate such tumor cells with metastatic potential. Here we will call this necrotic/hypoxic core the “aggressiveness niche” and will present data to support its involvement in generating these metastatic precursors. Within this niche, interaction of hypoxia-surviving cells with the inflammatory microenvironment influenced by newly recruited mesenchymal stromal cells (MSCs), tumor-associated macrophages (TAMs), and other types of cells and the establishment of bidirectional interactions between them elevate the aggressiveness of these tumor cells. Additionally, immune evasion properties induced in these cells most likely contribute in the formation and maintenance of such aggressiveness niche.