Inflammation-Driven Breast Tumor Cell Plasticity: Stemness/EMT, Therapy Resistance and Dormancy.
Inflammation-Driven Breast Tumor Cell Plasticity: Stemness/EMT, Therapy Resistance and Dormancy.
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DOI：
10.3389/fonc.2020.614468
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发表时间：
2020
影响因子：
4.7
通讯作者：
Ben-Baruch A
中科院分区：
文献类型：
--
作者：
Baram T;Rubinstein-Achiasaf L;Ben-Yaakov H;Ben-Baruch A
由于肿瘤细胞特性的不断变化，细胞异质性对癌症的治疗提出了巨大的挑战，赋予癌细胞在状态之间动态转换的能力。肿瘤内异质性主要由癌细胞可塑性驱动，这通过恶性细胞获得干细胞和上皮-间质转化（EMT）特性、发展治疗抗性和逃避休眠的能力来证明。癌细胞重塑的这些不同方面由内在和外在信号驱动，后者由肿瘤微环境的因素主导。作为肿瘤环境的一部分，慢性炎症通常被认为是支持肿瘤发展和进展的最有影响力的参与者。在这篇综述文章中，我们将最近的研究结果放在一起，研究炎症因子在推动肿瘤细胞可塑性关键过程中的作用。以乳腺癌为代表性研究系统，我们证明了炎症相关髓样细胞（主要是巨噬细胞）、促炎细胞因子[如肿瘤坏死因子α（TNFα）和白细胞介素6（IL-6）]和炎性趋化因子[主要是CXCL 8（白细胞介素8，IL-8）和CXCL 1（GROα）]在促进肿瘤细胞重塑中发挥的关键作用。这些炎症成分形成了一条共同的线索，参与调节三个可塑性水平：干性/EMT，治疗抗性和休眠。鉴于炎症因子是肿瘤细胞可塑性不同方面的共同特征，它们的靶向可能对癌症患者具有关键的临床益处。
Cellular heterogeneity poses an immense therapeutic challenge in cancer due to a constant change in tumor cell characteristics, endowing cancer cells with the ability to dynamically shift between states. Intra-tumor heterogeneity is largely driven by cancer cell plasticity, demonstrated by the ability of malignant cells to acquire stemness and epithelial-to-mesenchymal transition (EMT) properties, to develop therapy resistance and to escape dormancy. These different aspects of cancer cell remodeling are driven by intrinsic as well as by extrinsic signals, the latter being dominated by factors of the tumor microenvironment. As part of the tumor milieu, chronic inflammation is generally regarded as a most influential player that supports tumor development and progression. In this review article, we put together recent findings on the roles of inflammatory elements in driving forward key processes of tumor cell plasticity. Using breast cancer as a representative research system, we demonstrate the critical roles played by inflammation-associated myeloid cells (mainly macrophages), pro-inflammatory cytokines [such as tumor necrosis factor α (TNFα) and interleukin 6 (IL-6)] and inflammatory chemokines [primarily CXCL8 (interleukin 8, IL-8) and CXCL1 (GROα)] in promoting tumor cell remodeling. These inflammatory components form a common thread that is involved in regulation of the three plasticity levels: stemness/EMT, therapy resistance, and dormancy. In view of the fact that inflammatory elements are a common denominator shared by different aspects of tumor cell plasticity, it is possible that their targeting may have a critical clinical benefit for cancer patients.
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DOI：
10.1126/science.aao4227
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Albrengues J;Shields MA;Ng D;Park CG;Ambrico A;Poindexter ME;Upadhyay P;Uyeminami DL;Pommier A;Küttner V;Bružas E;Maiorino L;Bautista C;Carmona EM;Gimotty PA;Fearon DT;Chang K;Lyons SK;Pinkerton KE;Trotman LC;Goldberg MS;Yeh JT;Egeblad M
通讯作者：
Egeblad M
影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
5.6
作者：
Bent R;Moll L;Grabbe S;Bros M
通讯作者：
Bros M
影响因子：
4.2
作者：
Bhat K;Sarkissyan M;Wu Y;Vadgama JV
通讯作者：
Vadgama JV
影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J