Production of CCL20 from lung cancer cells induces the cell migration and proliferation through PI3K pathway.
Production of CCL20 from lung cancer cells induces the cell migration and proliferation through PI3K pathway.
复制标题
肺癌细胞产生的CCL20通过PI3K途径诱导细胞迁移和增殖
DOI：
10.1111/jcmm.12781
复制
发表时间：
2016-05
影响因子：
5.3
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Wang B;Shi L;Sun X;Wang L;Wang X;Chen C
肿瘤炎症微环境被认为在肿瘤细胞对治疗的敏感性和肺癌患者的预后中起作用。CCL 20是负责炎症细胞募集的关键化学引诱物之一，其表达已显示在多种肿瘤中过表达。本研究旨在研究人类非小细胞肺癌（NSCLC）中CCL 20功能和产生的潜在机制。检测非小细胞肺癌患者肺组织和非小细胞肺癌细胞（A549）中CCL 20基因和蛋白的表达。采用迁移试验和细胞存活监测系统，检测A549细胞中白细胞介素（IL）-1 β诱导的信号通路以及CCL 20诱导的A549细胞迁移和增殖的影响。并对CCL 20迁移过程中的信号转导机制进行了研究。我们最初发现，与正常肺样本相比，NSCLC肿瘤组织显著过表达CCL 20。此外，IL-1β可直接促进肺癌细胞中CCL 20的产生，这可被细胞外信号调节激酶（ERK）1/2抑制剂、p38丝裂原活化蛋白激酶（p38 MARP）抑制剂或PI 3 K抑制剂抑制。CCL 20通过激活ERK 1/2-MAPK和PI 3 K通路以自分泌方式促进肺癌细胞迁移和增殖。我们的数据表明，IL-1β可以通过激活MAPK和PI 3 K信号通路刺激肺癌细胞产生CCL 20，而CCL 20的自分泌可以通过激活ERK和PI 3 K信号通路促进肺癌细胞的迁移和增殖。我们的研究结果为CCL 20可能成为肺癌治疗的新靶点提供了新的证据。
Tumour inflammatory microenvironment is considered to play a role in the sensitivity of tumour cells to therapies and prognosis of patients with lung cancer. The expression of CCL20, one of the critical chemoattractants responsible for inflammation cells recruitment, has been shown overexpressed in variety of tumours. This study aimed at investigating potential mechanisms of CCL20 function and production in human non‐small cell lung cancer (NSCLC). Expression of CCL20 gene and protein in lung tissues of patients with NSCLC and NSCLC cells (A549) were determined. The interleukin (IL)‐1β‐induced signal pathways in A549 and the effect of CCL20‐induced A549 cell migration and proliferation were determined using migration assays and cell‐alive monitoring system. Mechanisms of signal pathways involved in the migration of CCL20 were also studied. We initially found that NSCLC tumour tissues markedly overexpressed CCL20 in comparison with normal lung samples. In addition, IL‐1β could directly promote CCL20 production in lung cancer cells, which was inhibited by extracellular signal‐regulated kinase (ERK)1/2 inhibitor, p38 mitogen‐activated protein kinase (p38 MARP) inhibitor or PI3K inhibitors. CCL20 promoted lung cancer cells migration and proliferation in an autocrine manner via activation of ERK1/2‐MAPK and PI3K pathways. Our data indicated that IL‐1β could stimulate CCL20 production from lung cancer cells through the activation of MAPKs and PI3K signal pathways, and the auto‐secretion of CCL20 could promote lung cancer cell migration and proliferation through the activation of ERK and PI3K signal pathways. Our results may provide a novel evidence that CCL20 could be a new therapeutic target for lung cancer.