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CXCR4 belongs to a family of G protein-coupled cell surface receptors and has been proved to a prognostic marker in a various tumors, including esophageal squamous cell cancer. In this study, we analyzed CXCR4 expression in tumor tissue and metastatic tumor tissues of lymph node by immunohistochemistry. CXCR4 was found to be an independent factor of patients' survival and heterogeneously expressed in tumor tissues. Compared with the primary tumor tissues, the scores of CXCR4 expression were significantly higher in corresponding metastatic tumor tissues of lymph nodes ( P < 0.01). It was suggested CXCR4-positive cells were prone to migrate to lymph nodes. In the further experiments in vitro, we confirmed heterogeneous expression of CXCR4 in esophageal squamous cell cancer cell lines ( KYSE70, Ec109, and CaES17) by flow cytometry analysis. Meanwhile, two subpopulations were isolated from Ec109 based on CXCR4 membrane expression by fluorescence-activated cell sorting. CXCR4-positive cells showed stronger migration ability in Boyden chamber assay than CXCR4 negative ones ( P < 0.01). However, no significant difference of cell proliferation was found between the two subpopulations in colony formation assay ( P > 0.05). We concluded that CXCR4 might be a key molecule in esophageal squamous cell cancer metastasis. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is a highly aggressive neoplasm with poor prognosis. The main reason for this disappointing outcome is the strong behavior of esophageal cancer cell's invasion and metastasis. CXC chemokine receptor 4 (CXCR4) was found to be expressed in many tumors and significantly correlated with invasion, angiogenesis, metastasis, and prognosis. In the present study, we investigated the expressions of CXCR4, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF) in esophageal squamous cell cancer (ESCC) and analyzed the relationship among the three proteins. Sections of paraffin-embedded tissues were obtained from 127 patients with ESCC undergoing esophagectomy at Zhongshan Hospital, Fudan University in 2005. The CXCR4, MMP-9, and VEGF expressions in EC tissues were evaluated according to the immunohistochemical staining area and intensity. The correlations between patients' prognosis and covariates were analyzed by Kaplan-Meier method (univariate analysis) and Cox regression (multivariate analysis). The overall expression rate of CXCR4, MMP-9, and VEGF was 88.2%, 93.7%, and 79.5%, respectively. CXCR4 expression was significantly associated with tumor grade, tumor size, tumor depth, regional lymph node metastasis, and tumor, node, metastasis (TNM) stage ( P < 0.05). MMP-9 expression was significantly associated with age and tumor grade ( P < 0.05). VEGF expression was significantly associated with tumor grade, tumor depth, and TNM stage ( P < 0.05). CXCR4 expression was positively correlated with MMP-9 expression ( P < 0.01, r= 0.365) and VEGF expression ( P < 0.01, r= 0.380). However, there was no significant correlation between MMP-9 and VEGF expression ( P > 0.05). In univariate analysis, CXCR4 expression, tumor size, tumor depth, lymph node metastasis, and TNM stage were correlated with patients' prognosis ( P < 0.05); in multivariate analysis, tumor size and lymph node metastasis were the independent factors of poor prognosis. CXCR4 was highly expressed in ESCC and correlated with MMP-9, VEGF, clinicopathological features and prognosis. We speculated CXCR4 play an important role during the progression of this disease and there might be some regulatory mechanism existing between CXCR4 and MMP-9/VEGF in ESCC. [ABSTRACT FROM AUTHOR]