Castration-refractory prostate cancer (CRPC) is treated with taxane-based 
chemotherapy, but eventually becomes drug resistant. It is thus essential to 
identify novel therapeutic targets for taxane resistance in CRPC patients. We 
investigated the role of the chemokine (C-C motif) receptor 1 (CCR1) and its 
ligand, chemokine (C-C motif) ligand 5 (CCL5), in taxane-resistant CRPC using 
paclitaxel-resistant prostate cancer cells (PC3PR) established from PC3 cells. 
We found that the expression levels of CCR1 mRNA and protein were up-regulated 
in PC3PR cells compared to PC3 cells. In order to investigate the role of 
increased CCR1 in PC3PR cells, we stimulated cells with CCL5, one of the 
chemokine ligands of CCR1. In CCL5-stimulated PC3PR cells, siRNA-mediated 
knockdown of CCR1 expression reduced phosphorylation of ERK1/2 and Rac1/cdc42. 
Furthermore, CCR1 knockdown and MEK1/2 inhibition decreased CCL5-stimulated 
secretion of MMPs 2 and 9, which play important roles in cancer cell invasion 
and metastasis. In the Matrigel invasion assay, knockdown of CCR1 and inhibition 
of the ERK and Rac signaling pathways significantly decreased the number of 
invading cells. Finally, the serum CCL5 protein level as measured by ELISA was 
not different among the three groups of patients: those with negative prostate 
biopsy, those at initial diagnosis of prostate cancer, and those with 
taxane-resistant prostate cancer. These results demonstrated for the first time 
that the interaction of CCR1 with CCL5 caused by increased expression of CCR1 
promotes invasion of PC3PR cells by increasing secretion of MMPs 2 and 9 and by 
activating ERK and Rac signaling. Our findings suggest that CCR1 could be a 
novel therapeutic target for taxane-resistant CRPC.