PMID- 33677254
OWN - NLM
STAT- MEDLINE
DCOM- 20210610
LR  - 20240226
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 95
DP  - 2021 Jun
TI  - Tumor-associated macrophages-mediated CXCL8 infiltration enhances breast cancer 
      metastasis: Suppression by Danirixin.
PG  - 107153
LID - S1567-5769(20)33620-1 [pii]
LID - 10.1016/j.intimp.2020.107153 [doi]
AB  - Breast cancer is the most frequent cancer among females and the second most 
      common cause of cancer deaths worldwide. Tumor-associated macrophages (TAMs) are 
      the most abundant immune cell population in the tumor microenvironment, including 
      breast cancer. Breast cancer stem cells (BCSCs) play an important role in 
      regulating breast cancer growth and metastasis, which still remains an obstacle 
      for successful treatment of breast cancer and requires further investigation, as 
      well as the potential therapeutic strategies. Cytokine array validated that C-X-C 
      motif chemokine ligand 8 (CXCL8) is a pivotal chemokine secreted by TAMs, and 
      CXCL8 could enhance breast cancer migration, invasion ability, and 
      epithelial-mesenchymal transition (EMT) in both animal and human breast cancer. 
      In this study, the clinical data firstly indicated that high CXCL8 expression was 
      significantly associated with metastasis and tumor growth in breast cancer 
      patients. Then, we showed that TAMs-released CXCL8 could markedly elevate the 
      migration, invasion and EMT events in breast cancer cells, as well as the 
      self-renewal of BCSCs in vitro. These processes were markedly abrogated by the 
      treatment of Danirixin, a reversible and selective antagonist of CXC chemokine 
      receptor 2 (CXCR2). Consistently, the in vivo analysis confirmed that CXCL8 
      suppression using Danirixin effectively reduced the tumor growth, lung metastasis 
      and repressed the self-renewal of BCSCs. Collectively, TAMs/CXCL8 could enhance 
      BCSCs self-renewal and breast cancer metastasis, and these effects could be 
      markedly abolished by Danirixin treatment, suppressing breast cancer progression 
      consequently. Therefore, Danirixin could be considered as a novel and effective 
      therapeutic strategy for breast cancer treatment without obvious toxicity to 
      major organs.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Nie, Gang
AU  - Nie G
AD  - Department of Breast Center, The Affiliated Hospital of Qingdao University, 
      Shandong 266000, China.
FAU - Cao, Xiangbo
AU  - Cao X
AD  - The Affiliated Hospital of Qingdao University, Library, Shandong 266000, China.
FAU - Mao, Yan
AU  - Mao Y
AD  - Department of Breast Center, The Affiliated Hospital of Qingdao University, 
      Shandong 266000, China.
FAU - Lv, Zhidong
AU  - Lv Z
AD  - Department of Breast Center, The Affiliated Hospital of Qingdao University, 
      Shandong 266000, China.
FAU - Lv, Meng
AU  - Lv M
AD  - Department of Breast Center, The Affiliated Hospital of Qingdao University, 
      Shandong 266000, China.
FAU - Wang, Yongmei
AU  - Wang Y
AD  - Department of Breast Center, The Affiliated Hospital of Qingdao University, 
      Shandong 266000, China.
FAU - Wang, Haibo
AU  - Wang H
AD  - Department of Breast Center, The Affiliated Hospital of Qingdao University, 
      Shandong 266000, China.
FAU - Liu, Chen
AU  - Liu C
AD  - Department of Breast Center, The Affiliated Hospital of Qingdao University, 
      Shandong 266000, China. Electronic address: liuchen.qduedu@foxmail.com.
LA  - eng
PT  - Journal Article
DEP - 20210305
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Interleukin-8)
RN  - 0 (Piperidines)
RN  - 0 (Sulfones)
RN  - R318PGH5VP (danirixin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Breast Neoplasms/blood/*drug therapy/immunology/pathology
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Epithelial-Mesenchymal Transition/drug effects
MH  - Female
MH  - Humans
MH  - Interleukin-8/blood/*immunology
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplastic Stem Cells/drug effects
MH  - Piperidines/pharmacology/*therapeutic use
MH  - Sulfones/pharmacology/*therapeutic use
MH  - Tumor-Associated Macrophages/*immunology
MH  - Mice
OTO - NOTNLM
OT  - BCSCs
OT  - Breast cancer
OT  - CXCL8
OT  - Danirixin
OT  - TAMs
EDAT- 2021/03/08 06:00
MHDA- 2021/06/11 06:00
CRDT- 2021/03/07 20:35
PHST- 2020/05/31 00:00 [received]
PHST- 2020/10/07 00:00 [revised]
PHST- 2020/10/21 00:00 [accepted]
PHST- 2021/03/08 06:00 [pubmed]
PHST- 2021/06/11 06:00 [medline]
PHST- 2021/03/07 20:35 [entrez]
AID - S1567-5769(20)33620-1 [pii]
AID - 10.1016/j.intimp.2020.107153 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2021 Jun;95:107153. doi: 10.1016/j.intimp.2020.107153. Epub 
      2021 Mar 5.