PMID- 29867925
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20190722
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Breast Cancer-Derived Exosomes Alter Macrophage Polarization via gp130/STAT3 
      Signaling.
PG  - 871
LID - 10.3389/fimmu.2018.00871 [doi]
LID - 871
AB  - Tumor-derived exosomes are being recognized as essential mediators of 
      intercellular communication between cancer and immune cells. It is well 
      established that bone marrow-derived macrophages (BMDMs) take up tumor-derived 
      exosomes. However, the functional impact of these exosomes on macrophage 
      phenotypes is controversial and not well studied. Here, we show that breast 
      cancer-derived exosomes alter the phenotype of macrophages through the 
      interleukin-6 (IL-6) receptor beta (glycoprotein 130, gp130)-STAT3 signaling 
      pathway. Addition of breast cancer-derived exosomes to macrophages results in the 
      activation of the IL-6 response pathway, including phosphorylation of the key 
      downstream transcription factor STAT3. Exosomal gp130, which is highly enriched 
      in cancer exosomes, triggers the secretion of IL-6 from BMDMs. Moreover, the 
      exposure of BMDMs to cancer-derived exosomes triggers changes from a conventional 
      toward a polarized phenotype often observed in tumor-associated macrophages. All 
      of these effects can be inhibited through the addition of a gp130 inhibitor to 
      cancer-derived exosomes or by blocking BMDMs exosome uptake. Collectively, this 
      work demonstrates that breast cancer-derived exosomes are capable of inducing 
      IL-6 secretion and a pro-survival phenotype in macrophages, partially via 
      gp130/STAT3 signaling.
FAU - Ham, Sunyoung
AU  - Ham S
AD  - Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, QLD, Australia.
AD  - Faculty of Health, School of Biomedical Sciences, Queensland University of 
      Technology, Brisbane, QLD, Australia.
FAU - Lima, Luize G
AU  - Lima LG
AD  - Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, QLD, Australia.
FAU - Chai, Edna Pei Zhi
AU  - Chai EPZ
AD  - Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, QLD, Australia.
AD  - Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
FAU - Muller, Alexandra
AU  - Muller A
AD  - Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, QLD, Australia.
AD  - Faculty of Medical Biology, University Duisburg-Essen, Essen, Germany.
FAU - Lobb, Richard J
AU  - Lobb RJ
AD  - Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, QLD, Australia.
AD  - Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
FAU - Krumeich, Sophie
AU  - Krumeich S
AD  - Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, QLD, Australia.
FAU - Wen, Shu Wen
AU  - Wen SW
AD  - Centre for Inflammatory Diseases, Department of Medicine, School of Clinical 
      Sciences, Monash University, Clayton, VIC, Australia.
FAU - Wiegmans, Adrian P
AU  - Wiegmans AP
AD  - Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, QLD, Australia.
FAU - Moller, Andreas
AU  - Moller A
AD  - Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, 
      Brisbane, QLD, Australia.
AD  - Faculty of Health, School of Biomedical Sciences, Queensland University of 
      Technology, Brisbane, QLD, Australia.
AD  - Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180508
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Hydrazines)
RN  - 0 (Il6st protein, mouse)
RN  - 0 (Interleukin-6)
RN  - 0 (N'-(7-fluoroH-pyrrolo(1,2-a)quinoxalin-4-yl)pyrazine-2-carbohydrazide)
RN  - 0 (Quinoxalines)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (interleukin-6, mouse)
RN  - 133483-10-0 (Cytokine Receptor gp130)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Cell Line, Tumor
MH  - Coculture Techniques
MH  - Cytokine Receptor gp130/antagonists & inhibitors/immunology/metabolism
MH  - Exosomes/drug effects/*immunology/metabolism
MH  - Female
MH  - Hydrazines/pharmacology
MH  - Interleukin-6/immunology/metabolism
MH  - Macrophage Activation/drug effects/immunology
MH  - Macrophages/cytology/*immunology/metabolism
MH  - Mammary Neoplasms, Experimental/*immunology/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Primary Cell Culture
MH  - Quinoxalines/pharmacology
MH  - STAT3 Transcription Factor/immunology/metabolism
MH  - Signal Transduction/drug effects/*immunology
MH  - Tumor Microenvironment/*immunology
PMC - PMC5951966
OTO - NOTNLM
OT  - STAT3
OT  - breast cancer
OT  - cancer-derived exosomes
OT  - glycoprotein 130
OT  - interleukin-6
OT  - tumor-associated macrophages
EDAT- 2018/06/06 06:00
MHDA- 2018/06/06 06:01
PMCR- 2018/01/01
CRDT- 2018/06/06 06:00
PHST- 2017/11/27 00:00 [received]
PHST- 2018/04/09 00:00 [accepted]
PHST- 2018/06/06 06:00 [entrez]
PHST- 2018/06/06 06:00 [pubmed]
PHST- 2018/06/06 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.00871 [doi]
PST - epublish
SO  - Front Immunol. 2018 May 8;9:871. doi: 10.3389/fimmu.2018.00871. eCollection 2018.