Interaction between human osteosarcoma and mesenchymal stem cells via an interleukin-8 signaling loop in the tumor microenvironment.
Interaction between human osteosarcoma and mesenchymal stem cells via an interleukin-8 signaling loop in the tumor microenvironment.
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DOI：
10.1186/s12964-018-0225-2
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发表时间：
2018-04-06
期刊：
影响因子：
--
通讯作者：
Tsumura H
中科院分区：
文献类型：
--
作者：
Kawano M;Tanaka K;Itonaga I;Iwasaki T;Tsumura H
骨肉瘤（Osteosarcoma， OS）是发病率最高的具有代表性的原发性骨恶性肿瘤。众所周知，OS的恶性表型，如增殖、侵袭和转移，不仅受到肿瘤本身特征的显著影响，还受到周围微环境的显著影响。换句话说，OS被认为是通过改变肿瘤附近细胞的特性来利用这些细胞。细胞间的直接接触被认为是造成这种现象的重要原因。在本研究中，我们假设体液因子介导的不需要细胞接触的相互作用可能在OS的进展中发挥重要作用。我们开发了一种新的共培养模型，使用OS细胞和间充质干细胞（MSCs）不进行细胞接触，发现两种细胞类型都高水平表达IL-8，并且OS细胞中的FAK在共培养条件下被磷酸化，导致肿瘤转移潜力增加。结果表明，OS细胞形成信号串讲回路，释放IL-8作为旁分泌因子，刺激MSCs表达IL-8，并接受MSCs释放的IL-8，加速IL-8在OS细胞中的表达。抗il -8抗体可抑制FAK表达及其下游信号传导，抑制OS细胞的侵袭潜能，导致转移灶减少。本研究不仅有助于阐明肿瘤侵袭转移的新分子机制，而且有助于开发阻断肿瘤中IL-8的新治疗策略。
Osteosarcoma (OS) is the representative primary malignant bone tumor with the highest incidence. It is known that malignant phenotypes of OS, such as proliferation, invasion, and metastasis, are significantly influenced not only by characteristics of the tumor itself, but also by the surrounding microenvironment. In other words, OS is considered to utilize cells in the vicinity of the tumor by changing the characteristics of these cells. Direct intercellular contact is believed to be important for this phenomenon. In the present study, we hypothesized that an interaction mediated by a humoral factor, requiring no cellular contact, might play a significant role in the progression of OS. We developed a new co-culture model, using OS cells and mesenchymal stem cells (MSCs) without cellular contact, and found that both cell types expressed IL-8 at a high level, and FAK in OS cells was phosphorylated leading to an increase in the metastatic potential of the tumor in the co-culture condition. It was revealed that OS cells formed a loop of signal cross-talk in which they released IL-8 as a paracrine factor, stimulating MSCs to express IL-8, and received IL-8 released by MSCs to accelerate IL-8 expression in OS cells. Administration of anti-IL-8 antibody resulted in the inhibition of FAK expression, its downstream signaling, and the invasive potential of the OS cells, resulting in decrease in metastatic lesions. The present study might lead not only to the clarification of a new molecular mechanism of invasion and metastasis of OS, but also to the development of a new therapeutic strategy of blocking IL-8 in OS.
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影响因子：
11.2
作者：
Liu S;Ginestier C;Ou SJ;Clouthier SG;Patel SH;Monville F;Korkaya H;Heath A;Dutcher J;Kleer CG;Jung Y;Dontu G;Taichman R;Wicha MS
通讯作者：
Wicha MS
影响因子：
--
作者：
Han S;Xu W;Wang Z;Qi X;Wang Y;Ni Y;Shen H;Hu Q;Han W
通讯作者：
Han W
影响因子：
21.3
作者：
Kajiro, Masashi;Hirota, Ryuichi;Yanagisawa, Junn
通讯作者：
Yanagisawa, Junn
DOI：
10.1158/1541-7786.mcr-12-0275
发表时间：
2012-10
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Bohrer LR;Schwertfeger KL
通讯作者：
Schwertfeger KL
影响因子：
8.8
作者：
Kitadai Y;Takahashi Y;Haruma K;Naka K;Sumii K;Yokozaki H;Yasui W;Mukaida N;Ohmoto Y;Kajiyama G;Fidler IJ;Tahara E
通讯作者：
Tahara E