Open AccessCXCL12‐Induced Angiogenesis in Laryngo‐Hypopharyngeal Squamous Cell Carcinoma
Author(s) -
Tan ChingTing,
Ko JenqYuh,
Li KaiChun,
Kuo MinLiang,
Huang YingHsuan
Publication year - 2011
Publication title -
otolaryngology–head and neck surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.232
H-Index - 121
eISSN - 1097-6817
pISSN - 0194-5998
DOI - 10.1177/0194599811415823a183
Subject(s) - angiogenesis , cancer research , signal transduction , cd31 , metastasis , protein kinase b , neovascularization , interleukin 8 , cxcr4 , chemokine , biology , medicine , cancer , immunology , receptor , microbiology and biotechnology , cytokine
Objective The success of solid tumor metastasis is dependent upon angiogenesis, and our previous result revealed that the CXCL12/CXCR4 axis could induce laryngeal and hypopharyngeal SCC (LHSCC) cells to produce angiogenic factors. Therefore, in this study, we will further elucidate the mechanisms of CXCL12‐induced angiogenesis in LHSCC cell lines. Method IHC staining and RT‐PCR were used to clarify the relationship of CXCR4 and angiogenesis. The Agilent oligoarray was used to study the angiogenesis profile, and investigate the relative contribution of different angiogenic factors. A mouse tumorigenicity model, the signal transduction pathways and the blocking effects of different antagonists were investigated. Results IHC staining and RT‐PCR revealed positive correlation of CXCR4 and CD31. Specific CXCR4 inhibitor AMD3100, neutralized antibody, 12G5, and shRNA could block the CXCL12‐induced angiogenesis. Agilent oligoarray and RT‐PCR discovered that CXCL12 induced IL‐8 expression. The expression could be blocked by specific CXCR4 inhibitors. Using IL‐8 neutralized antibody also effectively block the angiogenesis. Signal transduction study revealed that phosphorylation of Akt involved in the CXCL12/CXCR4 regulation of IL8 secretion. Conclusion Under such an investigation, a better understanding of angiogenic signaling and regulatory mechanisms in LHSCC were obtained and that may have benefit in searching for a new therapeutic agent to block this pathway as an adjuvant therapy for LHSCC might reduce the metastasis and improve the survival rates.