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01-02-2009 | Research Paper

Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone

Authors: Yi Lu, Qiuyan Chen, Eva Corey, Wen Xie, Jie Fan, Atsushi Mizokami, Jian Zhang

Published in: Clinical & Experimental Metastasis | Issue 2/2009

Abstract

Prostate cancer (PCa) frequently metastasizes to bone resulting in a mixture of osteolytic and osteoblastic lesions. We have previously reported that monocyte chemotactic protein-1 (MCP-1) is chemotactic for PCa cells, and its receptor, CCR2 expression, correlates with pathological stages. However, the role of MCP-1/CCR2 axis on PCa progression in bone remains unclear. We first evaluated the serum levels of MCP-1 in patients with bone metastases or localized PCa by enzyme-linked immunosorbent assay. We found that MCP-1 levels were elevated in patients with bone metastases compared to localized PCa. We further determined the effects of knockdown CCR2 or MCP-1 on PCa cell invasion and the tumor cell-induced osteoclast activity in vitro, respectively. PCa C4-2B and PC3 cells were transfected stably with either CCR2 short hairpin RNA (shRNA) or a scrambled RNA. CCR2 knockdown significantly diminished the MCP-1-induced PCa cell invasion. In addition, the MCP-1 production was knocked down by MCP-1 shRNA in C4-2B and PC3 cells. Conditioned media (CM) was collected and determined for the CM-induced osteoclast formation in vitro. MCP-1 knockdown significantly decreased the PCa CM-induced osteoclast formation. Finally, MCP-1 knockdown PC3 cells were implanted into the tibia of SCID mice for 4 weeks. Tumor volume was determined by histopathology and bone histomorphometry. MCP-1 knockdown diminished PC3 tumor growth in bone. We concluded that activation of MCP-1/CCR2 axis promotes PCa growth in bone. This study suggests that MCP-1 may be a target for PCa progression.

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Title: Activation of MCP-1/CCR2 axis promotes prostate cancer growth in bone
Authors: Yi Lu
Qiuyan Chen
Eva Corey
Wen Xie
Jie Fan
Atsushi Mizokami
Jian Zhang
Publication date: 01-02-2009
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 2/2009
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-008-9226-7

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