PMID- 23845726 OWN - NLM STAT- MEDLINE DCOM- 20131101 LR - 20220309 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1830 IP - 10 DP - 2013 Oct TI - CCL2 increases alphavbeta3 integrin expression and subsequently promotes prostate cancer migration. PG - 4917-27 LID - S0304-4165(13)00293-6 [pii] LID - 10.1016/j.bbagen.2013.06.033 [doi] AB - 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 PKCdelta 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 alphavbeta3. Treatment of cells with alphavbeta3 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 PKCdelta, 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 alphavbeta3 integrin production. GENERAL SIGNIFICANCE: CCL2 is a critical factor of prostate cancer metastasis. CI - (c) 2013. FAU - Lin, Tien-Huang AU - Lin TH AD - School of Chinese Medicine, China Medical University, Taichung, Taiwan. FAU - Liu, Hsin-Ho AU - Liu HH FAU - Tsai, Tsung-Hsun AU - Tsai TH FAU - Chen, Chi-Cheng AU - Chen CC FAU - Hsieh, Teng-Fu AU - Hsieh TF FAU - Lee, Shang-Sen AU - Lee SS FAU - Lee, Yuan-Ju AU - Lee YJ FAU - Chen, Wen-Chi AU - Chen WC FAU - Tang, Chih-Hsin AU - Tang CH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130709 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Integrin alphaVbeta3) SB - IM MH - Cell Line, Tumor MH - Chemokine CCL2/*metabolism MH - Humans MH - Integrin alphaVbeta3/*metabolism MH - Male MH - *Neoplasm Metastasis MH - Prostatic Neoplasms/*metabolism/pathology OTO - NOTNLM OT - CCL2 OT - CCR2 OT - Integrin OT - Migration OT - Prostate cancer EDAT- 2013/07/13 06:00 MHDA- 2013/11/02 06:00 CRDT- 2013/07/13 06:00 PHST- 2013/03/18 00:00 [received] PHST- 2013/05/20 00:00 [revised] PHST- 2013/06/28 00:00 [accepted] PHST- 2013/07/13 06:00 [entrez] PHST- 2013/07/13 06:00 [pubmed] PHST- 2013/11/02 06:00 [medline] AID - S0304-4165(13)00293-6 [pii] AID - 10.1016/j.bbagen.2013.06.033 [doi] PST - ppublish SO - Biochim Biophys Acta. 2013 Oct;1830(10):4917-27. doi: 10.1016/j.bbagen.2013.06.033. Epub 2013 Jul 9.