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Dis Esophagus. 2014 Apr;27(3):294-302. doi: 10.1111/dote.12100. Epub 2013 Jul 4.

CXCR4 heterogeneous expression in esophageal squamous cell cancer and stronger metastatic potential with CXCR4-positive cancer cells.

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Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.


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.


CXCR4; esophageal squamous cell cancer; heterogeneous expression; metastasis; migration

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