CCL2 increases αvβ3 integrin expression and subsequently promotes prostate cancer migration

Background: Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family which is associated with the disease status and outcomes of cancers. Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. However, the effect of CCL2 on human prostate cancer cells is largely unknown. The aim of this study was to examine the role of CCL2 in integrin expression and migratory activity in prostate cancers. Methods: Prostate cancer migration was examined using Transwell, wound healing, and invasion assay. The PKC delta and c-Src phosphorylations were examined by using western blotting. The qPCR was used to examine the mRNA expression of integrins. A transient transfection protocol was used to examine AP-1 activity. Results: Stimulation of prostate cancer cell lines (PC3, DU145, and LNCaP) induced migration and expression of integrin alpha v beta 3. Treatment of cells with alpha v beta 3 antibody or siRNA abolished CCL2-increased cell migration. CCL2-increased migration and integrin expression were diminished by CCR2 but not by CCR4 inhibitors, suggesting that the CCR2 receptor is involved in CCL2-promoted prostate cancer migration. CCL2 activated a signal transduction pathway that includes PKC delta, c-Src, and AP-1. Reagents that inhibit specific components of this pathway each diminished the ability of CCL2 to effect cell migration and integrin expression. Conclusions: Interaction between CCL2 and CCR2 enhances migration of prostate cancer cells through an increase in alpha v beta 3 integrin production. General significance: CCL2 is a critical factor of prostate cancer metastasis. (c) 2013 Elsevier B.V. All rights reserved.