Opposing Effects of Granulocyte Colony-Stimulating Factor on the Initiation and Progression of Breast Cancer Bone Metastases
Opposing Effects of Granulocyte Colony-Stimulating Factor on the Initiation and Progression of Breast Cancer Bone Metastases
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粒细胞集落刺激因子对乳腺癌骨转移的发生和进展的对抗作用
DOI：
10.1158/1541-7786.mcr-21-0243
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发表时间：
2021
影响因子：
5.2
通讯作者：
Mizoguchi Toshihide
中科院分区：
文献类型：
--
作者：
Hiraga Toru;Ito Susumu;Mizoguchi Toshihide
粒细胞集落刺激因子(G-CSF)是一种调节粒细胞生成的重要细胞因子，在相当大比例的乳腺癌中都有表达，并与肿瘤的进展密切相关。在这里，我们使用免疫活性的小鼠模型研究了G-CSF在乳腺癌骨转移发展中的作用。小鼠骨髓基质细胞中CXC趋化因子配体12(CXCL12)的表达明显减少，而CXCL12在维持造血干细胞和癌细胞向骨的归巢中起着关键作用。流式细胞仪分析显示，经G-CSF预处理的小鼠骨归巢癌细胞数量减少。G-CSF还能增加骨髓中髓系抑制细胞(MDSCs)的数量。使用抗Gr-1抗体治疗的MDSCs耗竭显著降低了骨转移瘤的负担。最后，采用两种不同的治疗方案，对G-CSF对骨转移瘤的整体疗效进行了研究。当小鼠在接种肿瘤细胞前给予G-CSF治疗时，G-CSF不改变骨转移-肿瘤负担。相反，当G-CSF在肿瘤细胞归巢到骨后开始治疗时，G-CSF显著加速了骨转移的形成。提示G-CSF通过下调CXCL12在骨髓基质细胞中的表达抑制癌细胞向骨的归巢，而G-CSF促进骨转移的发生至少部分是通过MDSC介导的机制。
Granulocyte colony stimulating factor (G-CSF), an essential cytokine regulating granulopoiesis, is expressed in a substantial proportion of breast cancers, and it has been implicated in cancer progression. Here, we examined effects of G-CSF on the development of bone metastases of breast cancer using immunocompetent mouse models. The expression of CXC chemokine ligand 12 (CXCL12) in bone marrow stromal cells, which plays a critical role in the maintenance of hematopoietic stem cells and also in cancer cell homing to bone, was markedly decreased in mice treated with G-CSF. Flow cytometric analysis revealed that pretreatment of mice with G-CSF reduced the number of bone-homing cancer cells. G-CSF also increased the population of myeloid-derived suppressor cells (MDSCs) in bone marrow. Depletion of MDSCs using anti–Gr-1 antibody treatment significantly decreased the metastatic tumor burden in bone. The overall effects of G-CSF on bone metastases were finally examined using two different treatment protocols. When mice were treated with G-CSF prior to the tumor cell inoculation, G-CSF did not change bone metastatic-tumor burden. In contrast, when G-CSF treatment was started after the tumor cells had homed to bone, G-CSF significantly accelerated bone metastases formation. These results suggest that G-CSF suppressed cancer cell homing to bone by downregulating CXCL12 expression in bone marrow stromal cells, whereas G-CSF stimulated the progression of bone metastases at least in part by MDSC-mediated mechanisms.ImplicationsG-CSF had opposing effects on the initiation and progression of bone metastases of breast cancer and the balance may regulate the metastatic tumor burden.
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影响因子：
11.2
作者：
C. J. Aslakson;F. Miller
通讯作者：
C. J. Aslakson;F. Miller
影响因子：
20.3
作者：
Hirbe, Angela C.;Uluckan, Ozge;Weilbaecher, Katherine
通讯作者：
Weilbaecher, Katherine
DOI：
10.1084/jem.20122252
发表时间：
2013-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pinho S;Lacombe J;Hanoun M;Mizoguchi T;Bruns I;Kunisaki Y;Frenette PS
通讯作者：
Frenette PS
影响因子：
15.9
作者：
Shiozawa, Yusuke;Pedersen, Elisabeth A.;Taichman, Russell S.
通讯作者：
Taichman, Russell S.
影响因子：
--
作者：
Huang, Jin-Feng;Shen, Jianfei;Wu, Aimin
通讯作者：
Wu, Aimin