Li Jianmin, Guan Jing, Long Xiaoping, Wang Yang, Xiang Xudong
Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
Department of Emergency Medicine, The First Hospital of Changsha, Changsha, Hunan 410005, P.R. China.
Oncol Rep. 2016 Jun;35(6):3523-31. doi: 10.3892/or.2016.4714. Epub 2016 Mar 29.
Lung cancer is the leading cause of cancer-related mortality in humans worldwide. Moreover, the overall 5-year survival rate is only 15%. Pathologically almost 80% of all lung cancer cases are non-small cell lung cancer (NSCLC). Cancer-associated fibroblasts (CAFs) have been found to exist in a large number of NSCLCs. CAFs have been proven to promote tumor progression, metastasis and resistance to therapy through paracrine effects in most solid tumors. In the present study, firstly we isolated CAFs from patient tissues and demonstrated that they promoted cell proliferation and chemoresistance to cisplatin in the lung cancer cell lines A549 and 95D in a paracrine manner. Secondly, using ELISA and quantative PCR, we found that a higher amount of stromal cell-derived factor 1 (SDF-1) existed in the CAFs rather than that observed in the normal fibroblasts (NFs). Thirdly, we detected that SDF-1 facilitated lung cancer cell proliferation and drug resistance via the CXCR4-mediated signaling pathway which involved NF-κB and Bcl-xL. Moreover, we also confirmed that the expression level of SDF-1 in the CAFs was negatively regulated by microRNA mir-1 through microRNA overexpression and quantitative PCR. Overall, our data provide one explanation for the effects of CAFs on lung cancer cells. Meanwhile, our results also suggest CAFs as a potential therapeutic target in tumor treatment.
肺癌是全球人类癌症相关死亡的主要原因。此外，总体5年生存率仅为15%。在病理上，几乎80%的肺癌病例是非小细胞肺癌（NSCLC）。已发现癌症相关成纤维细胞（CAF）大量存在于NSCLC中。在大多数实体瘤中，CAF已被证明通过旁分泌作用促进肿瘤进展、转移和对治疗的抗性。在本研究中，首先我们从患者组织中分离出CAF，并证明它们以旁分泌方式促进肺癌细胞系A549和95D中的细胞增殖和顺铂化疗抗性。其次，使用酶联免疫吸附测定（ELISA）和定量聚合酶链反应（PCR），我们发现CAF中存在的基质细胞衍生因子1（SDF-1）的量高于正常成纤维细胞（NF）。第三，我们检测到SDF-1通过涉及核因子κB（NF-κB）和Bcl-xL的CXCR4介导的信号通路促进肺癌细胞增殖和耐药性。此外，我们还通过微小RNA过表达和定量PCR证实，CAF中SDF-1的表达水平受微小RNA mir-1负调控。总体而言，我们的数据为CAF对肺癌细胞的作用提供了一种解释。同时，我们的结果也表明CAF作为肿瘤治疗中的潜在治疗靶点。
