title: Eotaxin-1 promotes prostate cancer cell invasion via activation of the CCR3-ERK pathway and upregulation of MMP-3 expression.
abstract: Chemokines have been reported to play crucial roles in tumor progression. Eotaxin-1 (CCL11), a member of the CC chemokine family, is elevated in many types of human cancer. Here, to reveal the molecular mechanisms of eotaxin-1 in prostate cancer cell invasion, the expression of eotaxin-1 receptors [CC chemokine receptor (CCR)2, CCR3 and CCR5] were silenced by small interfering RNA (siRNA). The ERK pathway was inhibited by the specific MEK inhibitor U0126. The role of eotaxin-1 and the CCR3-ERK pathway in prostate cancer cell invasion was assessed by invasion and migration assays. MMP-3 expression was detected by real-time PCR and ELISA assay. The results demonstrated that eotaxin-1 promoted the invasion and migration of DU-145 cells, and increased ERK1/2 activation and MMP-3 expression. Knockdown of CCR3 inhibited the invasion and migration of prostate cancer cells, and attenuated the eotaxin-1-induced ERK1/2 activation and MMP-3 expression. Furthermore, inactivation of the ERK pathway suppressed the eotaxin‑1-promoted invasion and migration, and decreased MMP-3 expression in the prostate cancer cells. Together, the present study suggests that eotaxin-1 increases MMP-3 expression via the CCR3-ERK pathway, thereby promoting prostate cancer cell invasion and migration. Thus, therapies that block eotaxin-1 and CCR3 may be effective interventions for prostate cancer.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, P.R. China.
authors.forename: Pei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Physiology, Xinxiang Medical College, Xinxiang, Henan 453003, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D054413:Chemokine CCL11 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D054390:Receptors, CCR2 / Q000235:genetics; D054397:Receptors, CCR3 / Q000235:genetics / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000235:genetics; D015854:Up-Regulation
chemical_list: D002070:Butadienes; C515456:CCL11 protein, human; C515334:CCR2 protein, human; C515350:CCR3 protein, human; C584933:CCR5 protein, human; D054413:Chemokine CCL11; D009570:Nitriles; D034741:RNA, Small Interfering; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D019278:Matrix Metalloproteinase 3