PMID- 29594759
OWN - NLM
STAT- MEDLINE
DCOM- 20190306
LR  - 20191218
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 170
IP  - 3
DP  - 2018 Aug
TI  - MCP-1 is overexpressed in triple-negative breast cancers and drives cancer 
      invasiveness and metastasis.
PG  - 477-486
LID - 10.1007/s10549-018-4760-8 [doi]
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive type of 
      breast cancer that lacks ER/PR and HER2 receptors. Hence, there is urgency in 
      developing new or novel therapeutic strategies for treatment of TNBC. Our study 
      shows that the Monocyte Chemoattractant Protein-1 (MCP-1) is a marker associated 
      with TNBC and may play a key role in TNBC disease progression. EXPERIMENTAL 
      DESIGN: ELISA method was used to measure secreted MCP-1, and mRNA levels were 
      determined by Real-time PCR in numerous cancer cell lines, representing various 
      breast cancer subtypes. Cellular invasiveness was determined by Boyden chamber 
      assay. RESULTS: Our data show that MCP-1 is upregulated in TNBC cell lines both 
      transcriptionally as well as in secreted protein levels compared to ER-positive 
      luminal cell line, MCF-7. Breast cancer patients, with Basal or Claudin-low 
      subtypes, also showed high expression of MCP-1. MCP-1 treatment induced cell 
      invasion in various breast cancer cell types, without affecting cell 
      proliferation. Small molecule antagonists against Chemokine Receptor 2 (CCR2), 
      cognate receptor for MCP-1 as well as the MAP kinase pathway inhibitor U0126 
      negatively affected MCP-1 induced MCF-7 cell invasion. This suggests that 
      MCP-1-CCR2 axis may regulate invasiveness via the MAP Kinase pathway. Knocking 
      down MCP-1 decreased cell invasion in TNBC cell line BT-549, along with 
      downregulation of key epithelial to mesenchymal transition markers, N-cadherin 
      and Vimentin. CONCLUSION: Our study suggests that MCP-1 mediated pathways could 
      be potential therapeutic targets for the treatment of TNBC, and could reduce 
      cancer health disparities.
FAU - Dutta, Pranabananda
AU  - Dutta P
AD  - Division of Cancer Research and Training, Department of Medicine, Charles R. Drew 
      University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 
      90059, USA.
FAU - Sarkissyan, Marianna
AU  - Sarkissyan M
AD  - Division of Cancer Research and Training, Department of Medicine, Charles R. Drew 
      University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 
      90059, USA.
FAU - Paico, Kimberly
AU  - Paico K
AD  - Division of Cancer Research and Training, Department of Medicine, Charles R. Drew 
      University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 
      90059, USA.
FAU - Wu, Yanyuan
AU  - Wu Y
AD  - Division of Cancer Research and Training, Department of Medicine, Charles R. Drew 
      University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 
      90059, USA.
AD  - Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University 
      of California at Los Angeles, Los Angeles, CA, USA.
FAU - Vadgama, Jaydutt V
AU  - Vadgama JV
AUID- ORCID: 0000-0002-0019-8622
AD  - Division of Cancer Research and Training, Department of Medicine, Charles R. Drew 
      University of Medicine and Science, 1731 East 120th Street, Los Angeles, CA, 
      90059, USA. jayvadgama@cdrewu.edu.
AD  - Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University 
      of California at Los Angeles, Los Angeles, CA, USA. jayvadgama@cdrewu.edu.
LA  - eng
GR  - U54 MD007598/MD/NIMHD NIH HHS/United States
GR  - U54 CA143930/CA/NCI NIH HHS/United States
GR  - U54 CA143931/CA/NCI NIH HHS/United States
GR  - 1U54CA14393/CA/NCI NIH HHS/United States
GR  - U54MD007598/MD/NIMHD NIH HHS/United States
PT  - Journal Article
DEP - 20180328
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - *Biomarkers, Tumor
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Female
MH  - *Gene Expression
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Matrix Metalloproteinase 9/genetics
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Models, Biological
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Phosphorylation
MH  - RNA, Small Interfering/genetics
MH  - Triple Negative Breast Neoplasms/*genetics/metabolism/*pathology
PMC - PMC6022526
OTO - NOTNLM
OT  - MAP kinase
OT  - MCP-1
OT  - Metastasis
OT  - TNBC
COIS- CONFLICT OF INTEREST: The authors declare that they have no conflict of interest. 
      ETHICAL STANDARDS: The experiments in this study comply with the current laws of 
      the country in which they were performed.
EDAT- 2018/03/30 06:00
MHDA- 2019/03/07 06:00
PMCR- 2018/03/28
CRDT- 2018/03/30 06:00
PHST- 2017/12/20 00:00 [received]
PHST- 2018/03/16 00:00 [accepted]
PHST- 2018/03/30 06:00 [pubmed]
PHST- 2019/03/07 06:00 [medline]
PHST- 2018/03/30 06:00 [entrez]
PHST- 2018/03/28 00:00 [pmc-release]
AID - 10.1007/s10549-018-4760-8 [pii]
AID - 4760 [pii]
AID - 10.1007/s10549-018-4760-8 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2018 Aug;170(3):477-486. doi: 10.1007/s10549-018-4760-8. 
      Epub 2018 Mar 28.