Abstract 1960: Upregulation of MCP-1 regulates invasiveness in triple negative breast cancer

Abstract

Abstract Background: Triple negative breast cancer (TNBC) poses a critical problem for targeted therapy due to lack of significant expression of estrogen, progesterone receptor or Her2/neu oncogene. Hence, it is imperative to identify novel therapeutic strategies to target TNBC. Our study is aimed to examine whether Monocyte Chemoattractant Protein -1 (MCP-1) is a specific marker for TNBC metastasis. Experimental Design: We employed ELISA to determine secreted MCP-1 in cell conditioned media, as well as Real-time PCR to determine the status of MCP-1 in TNBC cell lines. Boyden chamber assay was used to determine the effect of recombinant MCP-1 on cellular metastasis. Cellular proliferation was measured with MTT assay. Immunofluorescence staining was utilized for protein of interest in breast cancer cells. MCP-1 knockdown was performed using lentiviral vector with shRNA targeting MCP-1 coding regions. Results: Our data show that the key inflammatory chemokine MCP-1 is upregulated in TNBC cell lines both transcriptionally as well as in terms of secretion compared to ER-positive cell line, MCF-7. MCP-1 stimulation in MDA-MB231 and MCF-7cells does not affect cellular proliferation. However, MCP-1 enhances metastatic properties of MDA-MB-231 cells along with BT-549 cells. Inhibiting Chemokine receptor 2/4 (CCR2/4), cognate receptor for MCP-1, with small molecule antagonists negatively affects invasiveness in MDA-MB-231 cells as evidenced by Boyden chamber assay. Knocking down MCP-1 by shRNA decreases cell invasion in TNBC cell line, BT-549 along with downregulation of key epithelial to mesenchymal transition markers, N-cadherin and Vimentin. MCP-1 induced cell invasion in TNBC may involve activation of p44/p42 MAPK Thr202/Tyr204. Conclusion: Our study suggests that high MCP-1 levels in TNBC is driving up metastasis potential in cells. Thus MCP-1 and its mediated pathways could be potential therapeutic targets for the treatment of TNBC. Citation Format: Pranabananda Dutta, Kimberly Paico, Inez Yuwanita, Yanyuan Wu, Marianna Sarkissyan, Jaydutt Vadgama. Upregulation of MCP-1 regulates invasiveness in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1960. doi:10.1158/1538-7445.AM2017-1960