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CCR5 antagonist blocks metastasis of basal breast cancer cells
Journal article   Open access   Peer reviewed

CCR5 antagonist blocks metastasis of basal breast cancer cells

Marco Velasco-Velázquez, Xuanmao Jiao, Marisol De La Fuente, Timothy G Pestell, Adam Ertel, Michael P Lisanti and Richard G Pestell
Cancer research (Chicago, Ill.), v 72(15), pp 3839-3850
01 Aug 2012
DOI: https://doi.org/10.1158/0008-5472.CAN-11-3917
PMID: 22637726
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://figshare.com/articles/journal_contribution/Supplementary_Figure_2_from_CCR5_Antagonist_Blocks_Metastasis_of_Basal_Breast_Cancer_Cells/22393284View
SubmittedCC BY V4.0,  Open

Abstract

Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Breast Neoplasms - genetics Breast Neoplasms - pathology Breast Neoplasms - prevention & control CCR5 Receptor Antagonists Chemokine CCL5 - physiology Cyclohexanes - pharmacology Cyclohexanes - therapeutic use Female Gene Expression Regulation, Neoplastic - drug effects Humans Mice Mice, Inbred NOD Mice, SCID Neoplasm Metastasis Neoplasms, Basal Cell - genetics Neoplasms, Basal Cell - pathology Neoplasms, Basal Cell - prevention & control Piperazines - pharmacology Piperazines - therapeutic use Pyrimidines - pharmacology Pyrimidines - therapeutic use Receptors, CCR5 - genetics Receptors, CCR5 - metabolism Triazoles - pharmacology Triazoles - therapeutic use Tumor Cells, Cultured Xenograft Model Antitumor Assays
The roles of the chemokine CCL5 and its receptor CCR5 in breast cancer progression remain unclear. Here, we conducted microarray analysis on 2,254 human breast cancer specimens and found increased expression of CCL5 and its receptor CCR5, but not CCR3, in the basal and HER-2 genetic subtypes. The subpopulation of human breast cancer cell lines found to express CCR5 displayed a functional response to CCL5. In addition, oncogene transformation induced CCR5 expression, and the subpopulation of cells that expressed functional CCR5 also displayed increased invasiveness. The CCR5 antagonists maraviroc or vicriviroc, developed to block CCR5 HIV coreceptor function, reduced in vitro invasion of basal breast cancer cells without affecting cell proliferation or viability, and maraviroc decreased pulmonary metastasis in a preclinical mouse model of breast cancer. Taken together, our findings provide evidence for the key role of CCL5/CCR5 in the invasiveness of basal breast cancer cells and suggest that CCR5 antagonists may be used as an adjuvant therapy to reduce the risk of metastasis in patients with the basal breast cancer subtype.

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241 citations in Web of Science
244 citations in Scopus

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Oncology
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