PMID- 24548426
OWN - NLM
STAT- MEDLINE
DCOM- 20141008
LR  - 20211021
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 66
IP  - 1
DP  - 2014 Mar
TI  - Effects of the MCP-1 synthesis inhibitor bindarit on tumorigenesis and 
      inflammatory markers in the C3(1)/SV40Tag mouse model of breast cancer.
PG  - 60-8
LID - S1043-4666(13)00773-4 [pii]
LID - 10.1016/j.cyto.2013.12.011 [doi]
AB  - Breast cancer, the most deadly cancer in women, is characterized by elevated 
      levels of inflammation within and surrounding the tumor, which can lead to 
      accelerated growth, invasion and metastasis. Macrophages are central to the 
      inflammatory milieu and are recruited to the tumor microenvironment by several 
      factors including monocyte chemoattractant protein-1 (MCP-1). Using the 
      anti-inflammatory molecule bindarit to target MCP-1, we investigated the role of 
      this chemokine on macrophage related inflammation and mammary tumorigenesis in a 
      transgenic mouse model of breast cancer. C3(1)/SV40Tag mice and wild type FVB/N 
      were randomized to either control or 0.5% bindarit diet from 4 to 21weeks of age. 
      Tumor number and volume were recorded over time and at sacrifice. Macrophage 
      markers as well as inflammatory meditators were examined in the tumor tissue and 
      mammary glands. Circulating MCP-1 and IL-6 were measured by ELISA. Bindarit 
      treatment reduced tumor number (P<0.05), but did not affect tumor size, tumor 
      weight or tumor latency in C3(1)/SV40Tag mice. Within the tumor, mRNA expression 
      of bindarit's primary targets, MCP-1 and IL-12/p35, were significantly decreased 
      by bindarit treatment (P<0.05), and this was consistent with trends for reduced 
      expression of TNF-alpha, IL-6, F4/80, CD206, and IL-10. In mammary tissue, expression 
      of MCP-1, TNF-alpha, IL-6, F4/80, IL-10 and IL-12/p35 was significantly elevated in 
      C3(1)/SV40Tag mice compared to wild type FVB/N mice, but IL-6 was the only marker 
      decreased by bindarit treatment (P<0.05). Plasma MCP-1 was highly correlated with 
      tumor volume (P<0.05); however, it was not affected by bindarit at 21weeks of 
      age. Similarly, circulating IL-6 was increased in C3(1)/SV40Tag mice but there 
      was no effect of bindarit treatment. These results show that tumor multiplicity 
      in the C3(1)/SV40Tag mouse model of breast cancer is reduced by bindarit, however 
      these effects are independent of changes in plasma levels of MCP-1 and IL-6, but 
      may be related to the attenuated expression of MCP-1 along with several 
      inflammatory mediators and macrophage markers within the tumor.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Steiner, J L
AU  - Steiner JL
AD  - Department of Pathology Microbiology and Immunology, School of Medicine at South 
      Carolina, Columbia, SC 29209, United States; Department of Exercise Science, 
      University of South Carolina, Columbia, SC 29208, United States.
FAU - Davis, J M
AU  - Davis JM
AD  - Department of Exercise Science, University of South Carolina, Columbia, SC 29208, 
      United States.
FAU - McClellan, J L
AU  - McClellan JL
AD  - Department of Pathology Microbiology and Immunology, School of Medicine at South 
      Carolina, Columbia, SC 29209, United States; Department of Exercise Science, 
      University of South Carolina, Columbia, SC 29208, United States.
FAU - Guglielmotti, A
AU  - Guglielmotti A
AD  - Angelini, ACRAF, S. Palomba-Pomezia, Rome, Italy.
FAU - Murphy, E A
AU  - Murphy EA
AD  - Department of Pathology Microbiology and Immunology, School of Medicine at South 
      Carolina, Columbia, SC 29209, United States. Electronic address: 
      Angela.Murphy@uscmed.sc.edu.
LA  - eng
GR  - P20 GM103641/GM/NIGMS NIH HHS/United States
GR  - P20GM103641/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140120
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Antigens, Polyomavirus Transforming)
RN  - 0 (Biomarkers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Indazoles)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Propionates)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - JQ11LH711M (bindarit)
SB  - IM
MH  - Animals
MH  - Antigens, Polyomavirus Transforming/*metabolism
MH  - Biomarkers/blood
MH  - Body Weight/drug effects
MH  - Carcinogenesis/drug effects/*pathology
MH  - Chemokine CCL2/*antagonists & inhibitors/blood/metabolism
MH  - Disease Models, Animal
MH  - Feeding Behavior/drug effects
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Indazoles/pharmacology/*therapeutic use
MH  - Inflammation Mediators/*metabolism
MH  - Interleukin-6/blood/metabolism
MH  - Macrophages/drug effects/metabolism/pathology
MH  - Mammary Glands, Animal/drug effects/pathology
MH  - Mammary Neoplasms, Animal/blood/*drug therapy/*pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Organ Size/drug effects
MH  - Propionates/pharmacology/*therapeutic use
MH  - RNA, Messenger/genetics/metabolism
MH  - Spleen/drug effects/pathology
MH  - Tumor Burden/drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC4419732
MID - NIHMS552348
OTO - NOTNLM
OT  - Bindarit
OT  - C3(1)/SV40Tag transgenic mice
OT  - MCP-1
OT  - Mammary cancer
COIS- Conflicts of interest: None Declared.
EDAT- 2014/02/20 06:00
MHDA- 2014/10/09 06:00
PMCR- 2015/05/05
CRDT- 2014/02/20 06:00
PHST- 2013/04/04 00:00 [received]
PHST- 2013/11/14 00:00 [revised]
PHST- 2013/12/09 00:00 [accepted]
PHST- 2014/02/20 06:00 [entrez]
PHST- 2014/02/20 06:00 [pubmed]
PHST- 2014/10/09 06:00 [medline]
PHST- 2015/05/05 00:00 [pmc-release]
AID - S1043-4666(13)00773-4 [pii]
AID - 10.1016/j.cyto.2013.12.011 [doi]
PST - ppublish
SO  - Cytokine. 2014 Mar;66(1):60-8. doi: 10.1016/j.cyto.2013.12.011. Epub 2014 Jan 20.