TY - JOUR
T1 - CCR5 antagonist blocks metastasis of basal breast cancer cells
AU - Velasco-Velázquez, Marco
AU - Jiao, Xuanmao
AU - De La Fuente, Marisol
AU - Pestell, Timothy G.
AU - Ertel, Adam
AU - Lisanti, Michael P.
AU - Pestell, Richard G.
N1 - P30CA056036, NCI NIH HHS, United StatesR01CA070896, NCI NIH HHS, United StatesR01CA075503, NCI NIH HHS, United StatesR01CA086072, NCI NIH HHS, United StatesR01CA107382, NCI NIH HHS, United StatesR01CA120876, NCI NIH HHS, United StatesR01CA132115, NCI NIH HHS, United States
PY - 2012/8/1
Y1 - 2012/8/1
N2 - 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. ©2012 AACR.
AB - 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. ©2012 AACR.
U2 - 10.1158/0008-5472.CAN-11-3917
DO - 10.1158/0008-5472.CAN-11-3917
M3 - Article
C2 - 22637726
SN - 1538-7445
VL - 72
SP - 3839
EP - 3850
JO - Cancer Research
JF - Cancer Research
IS - 15
ER -
