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

被引:31
作者
Li, Kai-Chun [2 ]
Huang, Ying-Hsuan [1 ]
Ho, Ching-Yin [3 ,4 ]
Chu, Chia-Yu [5 ]
Cha, Shih-Ting [2 ]
Tsai, Hung-Huey [6 ,7 ]
Ko, Jenq-Yuh [1 ]
Chang, Cheng-Chi [8 ]
Tan, Ching-Ting [1 ]
机构
[1] Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan
[2] Natl Taiwan Univ, Coll Med, Grad Inst Toxicol, Taipei 10764, Taiwan
[3] Taipei Vet Gen Hosp, Dept Otolaryngol, Taipei, Taiwan
[4] Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan
[5] Natl Taiwan Univ Hosp, Dept Dermatol, Taipei, Taiwan
[6] Taipei Med Univ Hosp, Oral Rehabil Ctr Pediat Dent, Taipei, Taiwan
[7] Taipei Med Univ, Sch Oral Hyg, Coll Oral Med, Taipei, Taiwan
[8] Natl Taiwan Univ, Grad Inst Oral Biol, Taipei 10764, Taiwan
关键词
Laryngeal and hypopharyngeal squamous; cell carcinoma; Angiogenesis; SDF-1; alpha; CXCR4; IL-8; LYMPH-NODE METASTASIS; CXCR4; EXPRESSION; BREAST-CANCER; KAPPA-B; VEGF; ACTIVATION; PROGNOSIS; GROWTH;
D O I
10.1016/j.oraloncology.2012.01.006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:507 / 515
页数:9
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