Background: Inflammatory breast cancer (IBC) is a rare and highly metastatic variant of breast cancer with a poor prognosis and lower survival rate. The disease has a peculiar pattern of early recurrence to soft tissue, bone and central nervous system irrespective of molecular subtype. Currently, there are no specific therapeutic options for IBC patients, particularly there are no therapeutic agents aimed at controlling metastatic spread. Chemokine CCL5 and its receptor CCR5 play a significant role in breast cancer progression and metastasis. We have recently shown that CCR5 promotes breast cancer invasiveness and metastatic potential, and CCR5 inhibition by the FDA approved CCR5 antagonists Maraviroc and Vicriviroc reduced in vivo metastasis in a basal-like breast cancer model (Cancer Res 2012;72:3839-3850). Here, we examined the expression of CCR5, as well as the effects of CCR5 inhibition on the migration and invasion in vitro in human IBC cells.
Methods: IBC cell lines SUM149, SUM190, and FC-IBC-02 derived from pleural effusion fluid of an IBC patient were examined for the CCR5 expression by immunofluorescence staining. The effects of CCR5 antagonists (Maraviroc and Vicriviroc) on cell migration and invasion in vitro were examined using matrigel-coated Boyden chamber assay in FC-IBC-02 cells, which are triple-negative, basal-like, cancer stem cell phenotype, and rapidly developed primary tumors and metastasis in vivo (Breast Cancer Res Treat 2013;140:23–33). Cells were treated by Maraviroc and Vicriviroc at 100 µM.
Results: CCR5 was expressed at low positive component comprising only about 5-7 % of the total cell population in SUM 149 cells. CCR5 expression was not detected in SUM190 cells. CCR5 was expressed at significantly higher levels with a higher percentage of positive population (50-60%) in FC-IBC-02 cells compared with SUM149 cells. FC-IBC-02 cells have a relatively high percentage of CCR5 positive cells in suspension culture. CCR5 inhibition by both CCR5 antagonists Maraviroc and Vicriviroc significantly inhibited the migration and invasion of IBC cells in vitro. Maraviroc and Vicriviroc demonstrated effective agents in controlling migrations (55% and 60% relative inhibition).
Conclusions: CCR5 is highly expressed in human IBC cells. CCR5 antagonists demonstrated the inhibition of migration and invasion of IBC cells. Further studies are warranted to determine the effects of CCR5 antagonists in combination with standard treatment in the ability to control IBC progression and metastasis. These results may suggest a potential antimetastatic role for CCR5-inhibitors in IBC.
Citation Format: Zhaomei Mu, Xuanmao Jiao, Richard G Pestell, Massimo Cristofanilli. CCR5 antagonists suppresses the migration and invasion of human inflammatory breast cancer cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-14-06.