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Breast Cancer Res Treat. 2018 Aug;170(3):477-486. doi: 10.1007/s10549-018-4760-8. Epub 2018 Mar 28.

MCP-1 is overexpressed in triple-negative breast cancers and drives cancer invasiveness and metastasis.

Author information

1
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.
2
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
3
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.
4
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. jayvadgama@cdrewu.edu.

Abstract

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.

KEYWORDS:

MAP kinase; MCP-1; Metastasis; TNBC

PMID:
29594759
PMCID:
PMC6022526
DOI:
10.1007/s10549-018-4760-8
[Indexed for MEDLINE]
Free PMC Article

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