The role of IL-8 in the SDF-1α/CXCR4-induced angiogenesis of laryngeal and hypopharyngeal squamous cell carcinoma
Journal
Oral Oncology
Journal Volume
48
Journal Issue
6
Pages
507-515
Date Issued
2012
Author(s)
Abstract
Stromal cell-derived factor-1 (SDF-1) (CXCL12) has been observed to promote laryngeal and hypopharyngeal squamous cell carcinomas (LHSCCs) invasion through cooperation with its receptor CXCR4. Here, we further explore the angiogenesis mechanism induced by SDF-1/CXCR4 interaction in LHSCCs. Immunohistochemistry (IHC) reveals the significant correlation between CXCR4 and angiogenesis in tumors. After blocking the function of CXCR4 by specific inhibitor AMD3100 and neutralized antibody 12G5 or inhibiting the expression by siRNA, we were able to disrupt the HUVECs tube formation, demonstrating that SDF-1/CXCR4 indeed regulated the angiogenesis mechanism. The angiogenesis profiling from angiogenesis array and reverse transcription polymerase chain reaction indicates that IL-8 can be significantly triggered by SDF-1/CXCR4 interaction in LHSCCs. We also demonstrate that IL-8 secretion mechanism is regulated by Akt phosphorylation after SDF-1 stimulation. These results point out the importance of SDF-1/CXCR4 interaction in LHSCCs angiogenesis. The angiogenic factor IL-8 would be triggered by the cooperation of SDF-1 and CXCR4 through an Akt-dependent pathway. This provides a new targeting therapy utility, disrupting SDF-1/CXCR4 interaction combined with downstream-induced angiogenic factors in LHSCCs would be beneficial to improve clinical outcome. ? 2012 Elsevier Ltd. All rights reserved.
SDGs
Other Subjects
beta actin; chemokine receptor CXCR4; interleukin 6; interleukin 8; phosphatidylinositol 3 kinase; plerixafor; protein kinase B; small interfering RNA; stress activated protein kinase; stromal cell derived factor 1alpha; tissue inhibitor of metalloproteinase 1; tissue inhibitor of metalloproteinase 2; angiogenesis; article; clinical article; controlled study; cytokine release; disease association; human; human cell; human tissue; hypopharynx carcinoma; hypopharynx squamous cell carcinoma; immunohistochemistry; larynx squamous cell carcinoma; priority journal; protein expression; protein protein interaction; reverse transcription polymerase chain reaction; signal transduction; umbilical vein endothelial cell; upregulation; Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; Chemokine CXCL12; Humans; Hypopharyngeal Neoplasms; Interleukin-8; Laryngeal Neoplasms; Phosphorylation; Proto-Oncogene Proteins c-akt; Real-Time Polymerase Chain Reaction; Receptors, CXCR4; Reverse Transcriptase Polymerase Chain Reaction
Type
journal article