The role of IL-8 in the SDF-1α/CXCR4-induced angiogenesis of laryngeal and hypopharyngeal squamous cell carcinoma

Kai Chun Li, Ying Hsuan Huang, Ching Yin Ho, Chia Yu Chu, Shih Ting Cha, Hung Huey Tsai, Jenq Yuh Ko, Cheng Chi Chang, Ching Ting Tan

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)507-515
Number of pages9
JournalOral Oncology
Volume48
Issue number6
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Angiogenesis
  • CXCR4
  • IL-8
  • Laryngeal and hypopharyngeal squamous cell carcinoma
  • SDF-1α

ASJC Scopus subject areas

  • Oncology
  • Oral Surgery
  • Cancer Research

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    Li, K. C., Huang, Y. H., Ho, C. Y., Chu, C. Y., Cha, S. T., Tsai, H. H., Ko, J. Y., Chang, C. C., & Tan, C. T. (2012). The role of IL-8 in the SDF-1α/CXCR4-induced angiogenesis of laryngeal and hypopharyngeal squamous cell carcinoma. Oral Oncology, 48(6), 507-515. https://doi.org/10.1016/j.oraloncology.2012.01.006