Cancer ego-system in glioma: an iron-replenishing niche network systemically self-organized by cancer stem cells.

IF 5 3区 医学 Q2 IMMUNOLOGY
Kouichi Tabu, Tetsuya Taga
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引用次数: 3

Abstract

For all living organisms, the adaptation to outside environments is an essential determinant to survive natural and artificial selections and to sustain the whole ecosystem intact with functional biodiversity. Likewise, cancer cells have similar characteristics that evade not only stresses from the host-internal innate and adaptive immune systems but also those from host-externally administered therapeutic interventions. Such selfish characteristics of cancer cells lead to the formation of cancerous ecosystem with a wide variety of phenotypic heterogeneity, which should be called cancer "egosystem" from the host point of view. Recently increasing evidence demonstrates that cancer stem cells (CSCs) are responsible for this cancer egosystem by effectively exploiting host inflammatory and hematopoietic cells and thereby reconstructing their own advantageous niches, which may well be a driving force in cancer recurrence. CSCs are further likely to render multiple niches mutually interconnected and cooperating as a network to support back CSCs themselves. Here, we summarize a recently identified iron-replenishing niche network self-organized by glioma CSCs (GSCs) through remote regulation of host myeloid and erythroid lineage cells. GSCs recruit bone marrow (BM)-derived inflammatory monocytes into tumor parenchyma, facilitate their differentiation into macrophages (Mφs) and skew their polarization into pro-tumoral phenotype, i.e., tumor-associated Mφs (TAMs). Meanwhile, GSCs distantly enhance erythropoiesis in host hematopoietic organs like BM and spleen potentially by secreting some soluble mediators that maintain continuous supply of erythrocytes within tumors. In addition, as normal red pulp Mφs (RPMs) under steady state conditions in spleen recycle iron by phagocytosing the aged or damaged erythrocytes (a/dECs) and release it in time of need, TAMs at least in gliomas phagocytose the hemorrhaged erythrocytes within tumors and potentially serve as a source of iron, an important nutrient indispensable to GSC survival and glioma progression. Taken together, these studies provide the substantial evidence that CSCs have a unique strategy to orchestrate multiple niches as an ecosystem that threatens the host living, which in this sense must be an egosystem. Targeting such an adaptive subpopulation of CSCs could achieve drastic disturbance of the CSC niches and subsequent extinction of malignant neoplasms.

胶质瘤中的癌症自我系统:一个由癌症干细胞系统自组织的补铁生态位网络。
对于所有生物来说,适应外部环境是生存于自然和人为选择以及维持整个生态系统完整和功能性生物多样性的基本决定因素。同样,癌细胞也具有类似的特征,不仅可以逃避宿主内部固有免疫系统和适应性免疫系统的压力,还可以逃避宿主外部给予的治疗干预。癌细胞的这种自私自利的特性导致形成了具有多种表型异质性的癌变生态系统,从宿主的角度来看,这应该被称为癌症的“自我系统”。最近越来越多的证据表明,癌症干细胞(CSCs)通过有效地利用宿主的炎症细胞和造血细胞,从而重建自己的优势生态位,从而负责这种癌症自我系统,这很可能是癌症复发的驱动力。csc进一步有可能使多个利基相互联系并作为一个网络合作,以支持csc本身。在这里,我们总结了最近发现的一个由胶质瘤CSCs (GSCs)通过远程调节宿主髓系和红系细胞自我组织的补铁生态位网络。GSCs将骨髓(BM)来源的炎症单核细胞招募到肿瘤实质,促进其分化为巨噬细胞(m - φs),并使其极化为肿瘤前表型,即肿瘤相关的m - φs (tam)。同时,GSCs通过分泌一些可溶性介质,维持肿瘤内红细胞的持续供应,潜在地远距离促进宿主造血器官如骨髓和脾脏的红细胞生成。此外,在稳态条件下,正常的红浆Mφs (rpm)通过吞噬老化或受损的红细胞(a/dECs)在脾脏循环铁,并在需要时释放出来,tam至少在胶质瘤中吞噬肿瘤内的出血红细胞,并可能作为铁的来源,铁是GSC存活和胶质瘤进展所不可缺少的重要营养物质。综上所述,这些研究提供了大量证据,证明csc有一种独特的策略来协调多个生态位,作为一个威胁宿主生活的生态系统,从这个意义上说,宿主必须是一个自我系统。针对这样一个适应性的CSC亚群可以实现CSC生态位的剧烈干扰和随后的恶性肿瘤的灭绝。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
11.10
自引率
1.20%
发文量
45
审稿时长
11 weeks
期刊介绍: Inflammation and Regeneration is the official journal of the Japanese Society of Inflammation and Regeneration (JSIR). This journal provides an open access forum which covers a wide range of scientific topics in the basic and clinical researches on inflammation and regenerative medicine. It also covers investigations of infectious diseases, including COVID-19 and other emerging infectious diseases, which involve the inflammatory responses. Inflammation and Regeneration publishes papers in the following categories: research article, note, rapid communication, case report, review and clinical drug evaluation.
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