Role of CXCR4 in invasion and metastasis in esophageal cancer

应用免疫组织化学方法检测了CXCR4在人食管癌组织侵袭前沿的表达，发现其信号不仅定位于细胞质和细胞膜，而且定位于细胞核。支持这一发现，我们证实了CXCR4在单独分离的T.Tn EC细胞的细胞膜和细胞核的蛋白质组分中都有表达。此外，我们还探讨了CXCR4的免疫染色模式与EC临床病理特征的关系。接下来，我们检测了CXCR4配体SDF-1α和磷酸化的表皮生长因子受体在EC组织中的表达。有趣的是，核CXCR4核型的EC患者显著表达SDF-1a和核pEGFR。这些发现提示SDF-1a和/或EGF信号可能参与了EC细胞CXCR4的核表达。为了阐明EC细胞CXCR4核表达的调控因素，我们在低氧条件下培养了T.Tn EC细胞。低氧刺激使T.Tn EC细胞膜CXCR4表达增加，但核CXCR4表达减少。在未来的研究中，我们将阐明CXCR4在T.Tn EC细胞中的表达易位是否与侵袭或迁移等生物学变化有关。

We examined the expression of CXCR4 at the invasive front of human esophageal cancer (EC) tissues by immunohistochemistry and found that its signal is localized not only in the cytoplasm and cell membrane but also in the nucleus of EC cells. Supporting this finding, we confirmed that CXCR4 is expressed in both protein fractions of separately isolated cyto-membrane and nuclei from T.Tn EC cells. Moreover, we investigated the relationship between the immunostaining pattern of CXCR4 and clinicopathological features in patients with EC. Subsequently, we suggested that EC patients showing nuclear CXCR4 pattern had significantly worse prognosis.We next examined the expression of SDF-1α (ligand for CXCR4) and phosphorylated EGF receptor (pEGFR; candidate partner for signal closstalking) in EC tissues. Interestingly, EC patients with nuclear CXCR4 pattern significantly showed strong SDF-1a and nuclear pEGFR expression. These findings suggest that SDF-la and/or EGF signaling may be involved in the nuclear expression of CXCR4 in EC cells.To clarify the regulatory factor for nuclear CXCR4 expression in EC cells, we cultured T.Tn EC cells under hypoxic condition. Hypoxia stimulation enhanced membrane CXCR4 expression but reduced the nuclear ones in T.Tn EC cells. In the future studies, we will clarify whether the translocation of CXCR4 expression in T.Tn EC cells may be associated with the change of biology such as invasion or migration.