Zhang Ziqi, Sun Tong, Chen Yuxi, Gong Shu, Sun Xiye, Zou Fangdong, Peng Rui
1 West China School of Medicine, Sichuan University , Chengdu, People's Republic of China .
2 Key Laboratory of Bio-Resources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University , Chengdu, People's Republic of China .
DNA Cell Biol. 2016 Jul;35(7):348-57. doi: 10.1089/dna.2015.3104. Epub 2016 Mar 23.
Cancer is one of the most lethal diseases worldwide, and metastasis is the most common cause of patients' deaths. Identification and inhibition of markers involved in metastasis process in cancer cells are promising works to block metastasis and improve prognoses of patients. Chemokines are a superfamily of small, chemotactic cytokines, whose functions are based on interaction with corresponding receptors. It has been found that one of the functions of chemokines is to regulate migration and invasion abilities of lymphocytes, as well as cancer cells. Chemokine receptor 9 (CCR9) regulates trafficking of lymphocytes and cancer cell lines when interacting with its exclusive ligand chemokine 25 (CCL25). However, the mechanisms of CCL25/CCR9 signal that regulates metastasis of cancer cells are not completely known yet. In this study, we stimulated or inhibited CCL25/CCR9 signal in breast cancer cell line (MDA-MB-231) and hepatocellular cancer cell lines (HepG2 and HUH7), and found that CCL25/CCR9 signal resulted in different promotion of migration and invasion in different cell lines. These phenomena could be explained by selective regulation of several markers of epithelial-mesenchymal transition (EMT). Our findings suggested that CCL25/CCR9 signal may provide cancer cells with chemotactic abilities through influencing several EMT markers.
癌症是全球最致命的疾病之一，而转移是患者死亡的最常见原因。识别和抑制癌细胞转移过程中涉及的标志物是阻断转移并改善患者预后的有前景的工作。趋化因子是一类小的趋化细胞因子超家族，其功能基于与相应受体的相互作用。已发现趋化因子的功能之一是调节淋巴细胞以及癌细胞的迁移和侵袭能力。趋化因子受体9（CCR9）在与其唯一配体趋化因子25（CCL25）相互作用时调节淋巴细胞和癌细胞系的运输。然而，CCL25/CCR9信号调节癌细胞转移的机制尚未完全清楚。在本研究中，我们在乳腺癌细胞系（MDA-MB-231）和肝癌细胞系（HepG2和HUH7）中刺激或抑制CCL25/CCR9信号，发现CCL25/CCR9信号在不同细胞系中对迁移和侵袭有不同的促进作用。这些现象可以通过上皮-间质转化（EMT）的几种标志物的选择性调节来解释。我们的研究结果表明，CCL25/CCR9信号可能通过影响几种EMT标志物为癌细胞提供趋化能力。
