Division of Thoracic Surgery, University, Medical Centre Freiburg, Freiburg, Germany.
PLoS One. 2013;8(1):e53068. doi: 10.1371/journal.pone.0053068. Epub 2013 Jan 18.
Lung cancer is one of the leading causes of cancer related death worldwide with more than a million deaths per year. The poor prognosis is due to its high aggressiveness and its early metastasis. Although the exact mechanisms are still unknown, the process of epithelial to mesenchymal transition (EMT) seems to be involved in these neoplastic processes. We already demonstrated that serum levels of CCL18, a primate specific chemokine, are highly elevated in patients with lung cancer and correlate with their survival time of patients with adenocarcinoma of the lung. Therefore, we hypothesized that CCL18 may be directly involved in pathological processes of lung cancer, e.g. EMT. We investigated the effect of CCL18 on A549, an adenocarcinoma cell line of the lung, on EMT and other cell functions like proliferation, chemotaxis, invasion, chemoresistance and proliferation. Exposure of A549 lung cancer cells to CCL18 in various concentrations decreases the epithelial marker E-cadherin, whereas FSP-1, a marker of the mesenchymal phenotype increases. Accordingly, CCL18 induced the transcriptional EMT regulator SNAIL1 in a dose dependent fashion. In contrast, an increasing CCL18 concentration was associated with a decline of cell proliferation rate. In addition, CCL18 induced chemotaxis of these cells and increased their chemoresistance. Therefore, CCL18 may be an interesting therapeutic target for NSCLC.
肺癌是全球导致癌症相关死亡的主要原因之一，每年有超过 100 万人死亡。预后不良是由于其高度侵袭性和早期转移。尽管确切的机制尚不清楚，但上皮间质转化（EMT）过程似乎参与了这些肿瘤发生过程。我们已经证明，趋化因子 CCL18 的血清水平在肺癌患者中高度升高，并与肺腺癌患者的生存时间相关。因此，我们假设 CCL18 可能直接参与肺癌的病理过程，例如 EMT。我们研究了 CCL18 对 A549（一种肺腺癌细胞系）对 EMT 和其他细胞功能（如增殖、趋化性、侵袭、化疗耐药性和增殖）的影响。用不同浓度的 CCL18 处理 A549 肺癌细胞会降低上皮标志物 E-钙黏蛋白的表达，而 FSP-1（间充质表型的标志物）的表达增加。因此，CCL18 以剂量依赖的方式诱导转录 EMT 调节剂 SNAIL1。相反，CCL18 浓度的增加与细胞增殖率的下降相关。此外，CCL18 诱导这些细胞的趋化性并增加其化疗耐药性。因此，CCL18 可能是 NSCLC 的一个有趣的治疗靶点。
