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

Content Provider	Europe PMC
Author	Li, Yong-Chao Zou, Jiu-Ming Luo, Chao Shu, Yu Luo, Jing Qin, Jian Wang, Yu Li, Dong Wang, Shan-Shan Chi, Gang Guo, Fang Zhang, Gui-Mei Feng, Zuo-Hua
Copyright Year	2017
Abstract	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 anti-inflammatory 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.
Journal	Oncotarget
Volume Number	8
PubMed Central reference number	PMC5438660
Issue Number	17
PubMed reference number	28415700
e-ISSN	19492553
DOI	10.18632/oncotarget.16084
Language	English
Publisher	Impact Journals LLC
Publisher Date	2017-04-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: © 2017 Li et al.
Subject Keyword	circulating tumor cells (CTCs) disseminated carcinoma cells metastatic colonization inflammation neutrophils
Content Type	Text
Resource Type	Article
Subject	Oncology