Eotaxin-1 promotes prostate cancer cell invasion via activation of the CCR3-ERK pathway and upregulation of MMP-3 expression
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 eotaxin1-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.
Document Type: Research Article
Affiliations: 1: Department of Urology, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, P.R. China 2: Department of Urology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, P.R. China 3: Department of Physiology, Xinxiang Medical College, Xinxiang, Henan 453003, P.R. China
Publication date: 01 January 2014
- Oncology Reports is a monthly, peer-reviewed journal devoted to the publication of high quality original studies and reviews concerning a broad and comprehensive view of fundamental and applied research in oncology, focusing on carcinogenesis, metastasis and epidemiology.
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