Department of Pulmonary Medicine, The First affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
J Transl Med. 2014 Mar 16;12:70. doi: 10.1186/1479-5876-12-70.
Betacellulin (BTC), a member of the epidermal growth factor (EGF) family, binds and activates ErbB1 and ErbB4 homodimers. BTC was expressed in tumors and involved in tumor growth progression. CXCL8 (interleukin-8) was involved in tumor cell proliferation via the transactivation of the epidermal growth factor receptor (EGFR).
The present study was designed to investigate the possible interrelation between BTC and CXCL8 in human lung cancer cells (A549) and demonstrated the mechanisms of intracellular signals in the regulation of both functions. Bio-behaviors of A549 were assessed using Cell-IQ Alive Image Monitoring System.
We found that BTC significantly increased the production of CXCL8 through the activation of the EGFR-PI3K/Akt-Erk signal pathway. BTC induced the resistance of human lung cancer cells to TNF-α/CHX-induced apoptosis. Treatments with PI3K inhibitors, Erk1/2 inhibitor, or Erlotinib significantly inhibited BTC-induced CXCL8 production and cell proliferation and movement.
Our data indicated that CXCL8 production from lung cancer cells could be initiated by an autocrine mechanism or external sources of BTC through the EGFR-PI3K-Akt-Erk pathway to the formation of inflammatory microenvironment. BTC may act as a potential target to monitor and improve the development of lung cancer inflammation.
β细胞素（BTC）是表皮生长因子（EGF）家族的成员，可与 ErbB1 和 ErbB4 同源二聚体结合并激活它们。BTC 在肿瘤中表达，并参与肿瘤生长进展。CXCL8（白细胞介素-8）通过表皮生长因子受体（EGFR）的转激活参与肿瘤细胞增殖。
本研究旨在探讨人类肺癌细胞（A549）中 BTC 与 CXCL8 之间可能存在的相互关系，并阐明调节这两种功能的细胞内信号机制。使用 Cell-IQ 活细胞图像监测系统评估 A549 的生物行为。
我们发现 BTC 通过激活 EGFR-PI3K/Akt-Erk 信号通路显著增加 CXCL8 的产生。BTC 诱导人肺癌细胞对 TNF-α/CHX 诱导的凋亡产生抗性。PI3K 抑制剂、Erk1/2 抑制剂或厄洛替尼的处理显著抑制了 BTC 诱导的 CXCL8 产生以及细胞增殖和运动。
我们的数据表明，来自肺癌细胞的 CXCL8 产生可以通过自分泌机制或 BTC 的外部来源通过 EGFR-PI3K-Akt-Erk 通路启动，以形成炎症微环境。BTC 可能作为监测和改善肺癌炎症发展的潜在靶点。
