CXCL12‐Induced Angiogenesis in Laryngo‐Hypopharyngeal Squamous Cell Carcinoma

Abstract

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.