Circulating tumor cells promote the metastatic colonization of disseminated carcinoma cells by inducing systemic inflammation

被引：30

作者：

Li, Yong-Chao ^{[1
]}

Zou, Jiu-Ming ^{[1
]}

Luo, Chao ^{[1
]}

Shu, Yu ^{[1
]}

Luo, Jing ^{[1
]}

Qin, Jian ^{[1
]}

Wang, Yu ^{[1
]}

Li, Dong ^{[1
]}

Wang, Shan-Shan ^{[1
]}

Chi, Gang ^{[1
]}

Guo, Fang ^{[1
]}

Zhang, Gui-Mei ^{[1
]}

Feng, Zuo-Hua ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Biochem & Mol Biol, Wuhan 430030, Peoples R China

来源：

ONCOTARGET | 2017年 / 8卷 / 17期

基金：

中国国家自然科学基金;

关键词：

circulating tumor cells (CTCs); disseminated carcinoma cells; metastatic colonization; inflammation; neutrophils; BREAST-CANCER; IMMUNE-RESPONSES; STAT3; ACTIVATION; INNATE IMMUNITY; G-CSF; NEUTROPHILS; LUNG; PROGRESSION; EXPRESSION; MODEL;

D O I：

10.18632/oncotarget.16084

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Circulating tumor cells (CTCs) have been studied well in the prognosis for malignant diseases as liquid biopsy, but their contribution to tumor metastasis is not clearly defined. Here we report that CTCs could promote the metastatic colonization of disseminated carcinoma cells by inducing systemic inflammation and neutrophil recruitment to pre-metastatic organs. Depletion of neutrophils in vivo could effectively abrogate the promoting effect of CTCs on tumor cell metastasis. In the presence of CTCs, the pro-tumor function of neutrophils was augmented, whereas the antitumor function of neutrophils was suppressed. Mechanically, CTC-derived ligands for TLR2 and TLR4 (TLR2/4) induced the systemic inflammation, thus increasing the production of proinflammatory cytokines such as G-CSF and IL-6 that could induce the conversion of neutrophil function from tumor-suppressing to tumor-promoting. Moreover, CTCs induced the production of endogenous TLR2/4 ligands such as S100A8, S100A9, and SAA3, which may amplify the stimulating effect that induces the expression of proinflammatory cytokines. The promoting effect of CTCs on tumor cell metastasis could be abrogated by suppressing inflammatory response with IL-37, an antiinflammatory cytokine, or blocking CTC-derived ligands for TLR2/4. Identification of the metastatic axis of CTCs/systemic inflammation/neutrophils may provide potential targets for preventing tumor cell metastasis.

引用

页码：28418 / 28430

页数：13

共 56 条

[1] Rac2 is critical for neutrophil primary granule exocytosis [J].