The role of IL-8 in the SDF-1 alpha/CXCR4-induced angiogenesis of laryngeal and hypopharyngeal squamous cell carcinoma
Resource
Oral Oncol., 48(6), 507-515
Journal
Oral Oncol.
Journal Volume
48
Journal Issue
6
Pages
507-515
Date Issued
2012
Date
2012
Author(s)
Li, Kai-Chun
Huang, Ying-Hsuan
Ho, Ching-Yin
Chu, Chia-Yu
Cha, Shih-Ting
Tsai, Hung-Huey
Ko, Jenq-Yuh
Chang, Cheng-Chi
Tan, Ching-Ting
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. (C) 2012 Elsevier Ltd. All rights reserved.
Subjects
Laryngeal and hypopharyngeal squamous
cell carcinoma
Angiogenesis
SDF-1 alpha
CXCR4
IL-8
File(s)![Thumbnail Image]()
Loading...
Name
index.html
Size
23.2 KB
Format
HTML
Checksum
(MD5):130c4f73f8a268c390e3a71d3dbaf422