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: Feng Zhu, Pei Liu, Jun Li, Yan Zhang
• Journal: Oncology reports (Oncol Rep) Vol. 31 Issue 5 Pg. 2049-54 (May 2014) ISSN: 1791-2431 [Electronic] Greece
• PMID: 24604010 (Publication Type: Journal Article)

Chemical References

• Butadienes
• CCL11 protein, human
• CCR2 protein, human
• CCR3 protein, human
• CCR5 protein, human
• Chemokine CCL11
• Nitriles
• RNA, Small Interfering
• Receptors, CCR2
• Receptors, CCR3
• Receptors, CCR5
• U 0126
• Extracellular Signal-Regulated MAP Kinases
• Matrix Metalloproteinase 3

Topics

• Butadienes (pharmacology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Chemokine CCL11 (metabolism)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Humans
• MAP Kinase Signaling System
• Male
• Matrix Metalloproteinase 3 (biosynthesis)
• Neoplasm Invasiveness (genetics)
• Nitriles (pharmacology)
• Prostatic Neoplasms (pathology)
• RNA Interference
• RNA, Small Interfering
• Receptors, CCR2 (genetics)
• Receptors, CCR3 (genetics, metabolism)
• Receptors, CCR5 (genetics)
• Up-Regulation