IADR Abstract Archives
Opposite functions of CXCL14 and EGFR in oral squamous cell carcinoma
Objectives: Chemokine (C-X-C motif) ligand 14 (CXCL14) belongs to the CXC chemokine family. CXCL14 has been implicated in the maintenance of tissue macrophages, cancer progression, and metabolic regulation. CXCL14 expression is abundant in normal tissues. Interestingly, CXCL14 is downregulated in malignant cancers. Epidermal growth factor receptor (EGFR) signaling plays a crucial role in the aggressive features of human oral cancers. In this study, we examined the expression and methylation status of CXCL14 and its relationship with EGFR in human oral cancers.
Methods: Oral squamous cell carcinoma tissues were used for immunohistochemical analysis of CXCL14 and EGFR protein. Immunofluorescent staining of these tissues was also performed. CXCL14 mRNA expression was examined in oral squamous cell carcinoma cell lines by quantitative real-time PCR. Methylation specific PCR and bisulphite sequencing were also performed. Western blot analysis was performed in CXCL14 overexpressed oral cancer cells. Expression of CXCL14 and EGFR protein was also examined in a xenograft model treated with radiation.
Results: Immunohistochemical and immunofluorescence analysis revealed that there is an inverse relationship between CXCL14 and EGFR protein expression in human oral squamous cell carcinoma tissues. Irradiation induced CXCL14 protein expression and reduced expression of EGFR protein in xenografted human cancer cells. Forced expression of CXCL14 decreased CyclinD1 protein expression in oral cancer cells. Furthermore, hypermethylation of CXCL14 was detected in oral cancer cell lines.
Conclusions: Our results suggest that expression of CXL14 in human oral cancers might play a pivotal role in cancer progression. We propose that CXCL14 methylation might be the decisive factor for a CXCL14-targeted drug response in oral cancer.
Methods: Oral squamous cell carcinoma tissues were used for immunohistochemical analysis of CXCL14 and EGFR protein. Immunofluorescent staining of these tissues was also performed. CXCL14 mRNA expression was examined in oral squamous cell carcinoma cell lines by quantitative real-time PCR. Methylation specific PCR and bisulphite sequencing were also performed. Western blot analysis was performed in CXCL14 overexpressed oral cancer cells. Expression of CXCL14 and EGFR protein was also examined in a xenograft model treated with radiation.
Results: Immunohistochemical and immunofluorescence analysis revealed that there is an inverse relationship between CXCL14 and EGFR protein expression in human oral squamous cell carcinoma tissues. Irradiation induced CXCL14 protein expression and reduced expression of EGFR protein in xenografted human cancer cells. Forced expression of CXCL14 decreased CyclinD1 protein expression in oral cancer cells. Furthermore, hypermethylation of CXCL14 was detected in oral cancer cell lines.
Conclusions: Our results suggest that expression of CXL14 in human oral cancers might play a pivotal role in cancer progression. We propose that CXCL14 methylation might be the decisive factor for a CXCL14-targeted drug response in oral cancer.