PMID- 38355711
OWN - NLM
STAT- MEDLINE
DCOM- 20240216
LR  - 20240218
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 14
IP  - 1
DP  - 2024 Feb 15
TI  - Calcitriol promotes M2 polarization of tumor-associated macrophages in 4T1 mouse 
      mammary gland cancer via the induction of proinflammatory cytokines.
PG  - 3778
LID - 10.1038/s41598-024-54433-x [doi]
LID - 3778
AB  - Our research found that vitamin D(3) (VD(3)) treatment increased lung metastasis 
      in mice with 4T1 murine breast cancer (BC). This study aims to investigate the 
      impact of VD(3) on the activation of tumor-associated macrophages (TAMs) in BC. 
      Mice bearing 4T1, E0771, 67NR BC cells, and healthy mice, were fed diets with 
      varying VD(3) contents (100-deficient, 1000-normal, and 5000 IU/kg-elevated). 
      Some mice in the 1000 and 100 IU/kg groups received calcitriol. We studied bone 
      metastasis and characterized TAMs and bone marrow-derived macrophages (BMDMs). 
      4T1 cells had higher bone metastasis potential in the 5000 IU/kg and calcitriol 
      groups. In the same mice, an elevated tumor osteopontin level and M2 polarization 
      of TAMs (MHCII(low) CD44(high) phenotype) were observed. Gene expression analysis 
      confirmed M2 polarization of 4T1 (but not 67NR) TAMs and BMDMs, particularly in 
      the 100 IU + cal group (increased Mrc1, Il23, and Il6). This polarization was 
      likely due to COX-2/PGE(2) induction in 4T1 calcitriol-treated cells, leading to 
      increased proinflammatory cytokines like IL-6 and IL-23. Future studies will 
      explore COX-2/PGE(2) as a primary mediator of calcitriol-stimulated inflammation 
      in the BC microenvironment, especially relevant for BC patients with VD(3) 
      deficiency and supplementation.
CI  - (c) 2024. The Author(s).
FAU - Stachowicz-Suhs, Martyna
AU  - Stachowicz-Suhs M
AD  - Department of Experimental Oncology, Hirszfeld Institute of Immunology and 
      Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland.
FAU - Labedz, Natalia
AU  - Labedz N
AD  - Department of Experimental Oncology, Hirszfeld Institute of Immunology and 
      Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland.
FAU - Anisiewicz, Artur
AU  - Anisiewicz A
AD  - Department of Experimental Oncology, Hirszfeld Institute of Immunology and 
      Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland.
FAU - Banach, Joanna
AU  - Banach J
AD  - Department of Experimental Oncology, Hirszfeld Institute of Immunology and 
      Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland.
FAU - Klopotowska, Dagmara
AU  - Klopotowska D
AD  - Department of Experimental Oncology, Hirszfeld Institute of Immunology and 
      Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland.
FAU - Milczarek, Magdalena
AU  - Milczarek M
AD  - Department of Experimental Oncology, Hirszfeld Institute of Immunology and 
      Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland.
FAU - Piotrowska, Aleksandra
AU  - Piotrowska A
AD  - Division of Histology and Embryology, Department of Human Morphology and 
      Embryology, Faculty of Medicine, Wroclaw Medical University, Chalubinskiego 6a, 
      50-368, Wroclaw, Poland.
FAU - Dziegiel, Piotr
AU  - Dziegiel P
AD  - Division of Histology and Embryology, Department of Human Morphology and 
      Embryology, Faculty of Medicine, Wroclaw Medical University, Chalubinskiego 6a, 
      50-368, Wroclaw, Poland.
FAU - Maciejczyk, Adam
AU  - Maciejczyk A
AD  - Department of Oncology, Wroclaw Medical University, Pl. Ludwika Hirszfelda 12, 
      53-413, Wroclaw, Poland.
AD  - Lower Silesian Oncology, Pulmonology and Hematology Center, Pl. Ludwika 
      Hirszfelda 12, 53-413, Wroclaw, Poland.
FAU - Matkowski, Rafal
AU  - Matkowski R
AD  - Department of Oncology, Wroclaw Medical University, Pl. Ludwika Hirszfelda 12, 
      53-413, Wroclaw, Poland.
AD  - Lower Silesian Oncology, Pulmonology and Hematology Center, Pl. Ludwika 
      Hirszfelda 12, 53-413, Wroclaw, Poland.
FAU - Wietrzyk, Joanna
AU  - Wietrzyk J
AD  - Department of Experimental Oncology, Hirszfeld Institute of Immunology and 
      Experimental Therapy, Weigla 12, 53-114, Wroclaw, Poland. 
      joanna.wietrzyk@hirszfeld.pl.
LA  - eng
GR  - 2017/27/B/NZ5/01167/Narodowe Centrum Nauki/
PT  - Journal Article
DEP - 20240215
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cytokines)
RN  - FXC9231JVH (Calcitriol)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - Female
MH  - Cytokines/metabolism
MH  - Calcitriol/pharmacology
MH  - Tumor-Associated Macrophages/metabolism
MH  - Cyclooxygenase 2/genetics
MH  - *Mammary Glands, Human/metabolism
MH  - Cell Line, Tumor
MH  - *Breast Neoplasms/pathology
MH  - Tumor Microenvironment
PMC - PMC10866890
COIS- The authors declare no competing interests.
EDAT- 2024/02/15 00:42
MHDA- 2024/02/16 06:43
PMCR- 2024/02/15
CRDT- 2024/02/14 23:50
PHST- 2023/10/31 00:00 [received]
PHST- 2024/02/13 00:00 [accepted]
PHST- 2024/02/16 06:43 [medline]
PHST- 2024/02/15 00:42 [pubmed]
PHST- 2024/02/14 23:50 [entrez]
PHST- 2024/02/15 00:00 [pmc-release]
AID - 10.1038/s41598-024-54433-x [pii]
AID - 54433 [pii]
AID - 10.1038/s41598-024-54433-x [doi]
PST - epublish
SO  - Sci Rep. 2024 Feb 15;14(1):3778. doi: 10.1038/s41598-024-54433-x.