Expression and clinical significance of hypoxia inducible factor-1 a and chemokine receptor 4 in esophageal squamous carcinoma

Abstract

Objective To observe the expression of hypoxia inducible factor-1α (HIF-1α) and chemokine receptor 4 (CXCR4) in Caes-17 cells under hypoxia,and investigate the expression and clinical significance of HIF-1 α and CXCR4 in esophageal squamous cell carcinoma (ESCC) tissues and their correlation.Methods Caes-17 cells were cultured in vitro.The expression of HIF-1α and CXCR4 was detected by using fluorescence real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting under normoxia or hypoxia.The expressions of HIF-1α and CXCR4 protein was assessed by using immunohistochemistry in 106 cases of ESCC specimens with complete clinical and pathological date and 30 cases of normal esophageal mucosa tissues.The relationship between HIF-1 α or CXCR4 and pathologic features of esophageal cancer was analyzed.The correlation between HIF-1α and CXCR4 was also assessed.Results The expression of HIF-1α protein (0.86 ±0.03),CXCR4 mRNA (6.95 ±0.30),CXCR4 protein (0.56 ± 0.02) were increased under hypoxia than those under normoxia [HIF-1 α protein (0.28±0.04),CXCR4 mRNA (1.09±0.14),CXCR4 protein (0.11±0.03)] (P＜0.05).There was no significant difference in HIF-1 α mRNA (0.96 ± 0.06) between hypoxia and normoxia (1.14 ± 0.12) (P ＞ 0.05).The positive rate of HIF-1α and CXCR4 expression in ESCC tissues was obviously higher than that in normal esophageal mucosa tissues (P ＜ 0.05).The expression of HIF-1 α in ESCC tissues was associated with depth of tumor invasion,lymph node metastasis and TNM stage (P ＜ 0.05) and the expression of CXCR4 in ESCC tissues was associated with depth of tumor invasion,lymph node metastasis (P ＜ 0.05).The expression of CXCR4 was significantly correlated with the expression of HIF-1α(r =0.539,P ＜ 0.05).Conclusion Hypoxia can increase the expression level of HIF-1 α and CXCR4 in esophageal cancer cells.The CXCR4 expression has a significantly positive correlation with the HIF-1α expression in esophageal cancer.They may play synergetic roles in the genesis,development,invasion and metastasis of ESCC. Key words: Esophageal squamous carcinoma; Hypoxia; Hypoxia inducible factor-1 α; Chemokine receptor 4 ; Immunohistochemistry