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Breast Cancer Research and Treatment

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Open Access 01-08-2018 | Preclinical study

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

Authors: Pranabananda Dutta, Marianna Sarkissyan, Kimberly Paico, Yanyuan Wu, Jaydutt V. Vadgama

Published in: Breast Cancer Research and Treatment | Issue 3/2018

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.

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Title: MCP-1 is overexpressed in triple-negative breast cancers and drives cancer invasiveness and metastasis
Authors: Pranabananda Dutta
Marianna Sarkissyan
Kimberly Paico
Yanyuan Wu
Jaydutt V. Vadgama
Publication date: 01-08-2018
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2018
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4760-8

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