PMID- 34174813
OWN - NLM
STAT- MEDLINE
DCOM- 20211223
LR  - 20240226
IS  - 1689-1392 (Electronic)
IS  - 1425-8153 (Print)
IS  - 1425-8153 (Linking)
VI  - 26
IP  - 1
DP  - 2021 Jun 26
TI  - Macrophage polarization by MSC-derived CXCL12 determines tumor growth.
PG  - 30
LID - 10.1186/s11658-021-00273-w [doi]
LID - 30
AB  - BACKGROUND: Phenotypic and functional heterogeneity of macrophages is known to be 
      the main reason for their ability to regulate inflammation and promote 
      tumorigenesis. Mesenchymal stem cells (MSCs) are one of the principal cells 
      commonly found in the tumor stromal niche, with capability of macrophage 
      phenotypic switching. The objective of this study was to evaluate the role of 
      C-X-C motif chemokine ligand 12 (CXCL12) produced by marrow-derived MSCs in the 
      phenotypic and functional pattern of bone marrow-derived macrophages (BMDMs). 
      METHODS: First, the CRISPR/Cas9 system was used for the CXCL12 gene knock-out in 
      MSCs. Then, coculture systems were used to investigate the role of 
      MSCs(CXCL12-/-) and MSCs(CXCL12+/+) in determination of macrophage phenotype. To 
      further analyze the role of the MSC-derived CXCL12 niche, cocultures of 4T1 
      mammary tumor cells and macrophages primed with MSCs(CXCL12-/-) or 
      MSCs(CXCL12+/+) as well as in-vivo limiting dilution assays were performed. 
      RESULTS: Our results revealed that the expression of IL-4, IL-10, TGF-beta and CD206 
      as M2 markers was significantly increased in macrophages co-cultured with 
      MSCs(CXCL12+/+) , whereas the expression of IL-6, TNF-alpha and iNOS was conversely 
      decreased. The number and size of multicellular tumor spheroids were remarkably 
      higher when 4T1 cells were cocultured with MSC(CXCL12+/+)-induced M2 macrophages. 
      We also found that the occurrence of tumors was significantly higher in 
      coinjection of 4T1 cells with MSC(CXCL12+/+)-primed macrophages. Tumor initiating 
      cells were significantly decreased after coinjection of 4T1 cells with 
      macrophages pretreated with MSCs(CXCL12-/-). CONCLUSIONS: In conclusion, our 
      findings shed new light on the role of MSC-derived CXCL12 in macrophage 
      phenotypic switching to M2, affecting their function in tumorigenesis.
FAU - Babazadeh, Shabnam
AU  - Babazadeh S
AD  - Department of Clinical Pathology, Faculty of Veterinary Medicine, University of 
      Tehran, Tehran, Iran.
FAU - Nassiri, Seyed Mahdi
AU  - Nassiri SM
AUID- ORCID: 0000-0002-5746-9593
AD  - Department of Clinical Pathology, Faculty of Veterinary Medicine, University of 
      Tehran, Tehran, Iran. nasirim@ut.ac.ir.
FAU - Siavashi, Vahid
AU  - Siavashi V
AD  - Department of Clinical Pathology, Faculty of Veterinary Medicine, University of 
      Tehran, Tehran, Iran.
FAU - Sahlabadi, Mohadeseh
AU  - Sahlabadi M
AD  - Department of Clinical Pathology, Faculty of Veterinary Medicine, University of 
      Tehran, Tehran, Iran.
FAU - Hajinasrollah, Mostafa
AU  - Hajinasrollah M
AD  - Department of Stem Cells and Developmental Biology at Cell Science Research 
      Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, 
      Iran.
FAU - Zamani-Ahmadmahmudi, Mohamad
AU  - Zamani-Ahmadmahmudi M
AD  - Department of Clinical Science, Faculty of Veterinary Medicine, Shahid Bahonar 
      University of Kerman, Kerman, Iran.
LA  - eng
PT  - Journal Article
DEP - 20210626
PL  - England
TA  - Cell Mol Biol Lett
JT  - Cellular & molecular biology letters
JID - 9607427
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcl12 protein, mouse)
SB  - IM
MH  - Animals
MH  - Carcinogenesis/immunology/pathology
MH  - Cells, Cultured
MH  - Chemokine CXCL12/*immunology
MH  - Female
MH  - *Macrophage Activation
MH  - Macrophages/*immunology/pathology
MH  - Mesenchymal Stem Cells/*immunology/pathology
MH  - Mice, Inbred BALB C
MH  - Neoplasms/*immunology/pathology
MH  - Mice
PMC - PMC8236206
OTO - NOTNLM
OT  - C-X-C motif chemokine ligand 12 (CXCL12)
OT  - Cytokine
OT  - Macrophage
OT  - Mesenchymal stem cells (MSCs)
OT  - Phagocytosis
OT  - Tumor microenvironment
COIS- The authors declare that they have no conflicts of interest with the contents of 
      this article.
EDAT- 2021/06/28 06:00
MHDA- 2021/12/24 06:00
PMCR- 2021/06/26
CRDT- 2021/06/27 20:22
PHST- 2021/03/10 00:00 [received]
PHST- 2021/06/15 00:00 [accepted]
PHST- 2021/06/27 20:22 [entrez]
PHST- 2021/06/28 06:00 [pubmed]
PHST- 2021/12/24 06:00 [medline]
PHST- 2021/06/26 00:00 [pmc-release]
AID - 10.1186/s11658-021-00273-w [pii]
AID - 273 [pii]
AID - 10.1186/s11658-021-00273-w [doi]
PST - epublish
SO  - Cell Mol Biol Lett. 2021 Jun 26;26(1):30. doi: 10.1186/s11658-021-00273-w.