Effect of CXCL12/CXCR4 on increasing the metastatic potential of non-small cell lung cancer in vitro is inhibited through the downregulation of CXCR4 chemokine receptor expression.

Songping Xie,Bangchang Cheng,Guohua Fan,Jie Huang,Ping Dong,Ganjun Kang,Wei Wang,Wenhui Zeng,Qing Geng

doi:10.3892/ol.2014.1837

Songping Xie, Bangchang Cheng + Show 7 more

Open Access

https://doi.org/10.3892/ol.2014.1837

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Abstract

Lung cancer ranks as the most common type of cancer in males worldwide. Although great advances have been achieved in chemotherapy and radiotherapy, the long-term survival rate of lung cancer patients has not improved significantly. Dissemination of lung cancer in the thoracic cavity and metastatic spread to the liver, bone and brain are characteristic of non-small cell lung cancer (NSCLC), constituting the primary source of morbidity and mortality in lung cancer. Increasing evidence also indicates that the CXC chemokine receptor 4 (CXCR4)/chemokine CXC motif ligand 12 (CXCL12) chemokine axis is important for the cell invasion and migration of lung cancer. CXCR4 is a G protein-coupled receptor with a major role in lymphocyte homing. Its ligand, CXCL12, is secreted by target organs and functions as a highly efficient chemotactic factor for T cells, monocytes, pre-B cells, dendritic cells and myeloid bone marrow-derived cells. In the current study, recombinant CXCR4-specific small interfering RNA-pBSilence1.1 plasmids were constructed and transfected into the A549 NSCLC cell line in vitro. Reverse transcription polymerase chain reaction and western blotting revealed that CXCR4 was downregulated in transfected cells compared with control cells. The results of MTT and Transwell migration assays indicated that the specific downregulation of CXCR4 inhibited cell growth, invasiveness and migration. Thus, siRNA targeting of CXCR4 may effectively inhibit the effect of CXCL12/CXCR4 on increasing the metastatic potential of NSCLC.

Highlights

Lung cancer ranks as the most frequent type of cancer in males worldwide with increasing incidence rates according to the epidemiology data [1]
There is increasing evidence to suggest that the CXC motif ligand 12 (CXCL12)/CXC chemokine receptor 4 (CXCR4) chemokine axis is important for the cell invasion and migration of several types of tumor, lung cancer
It has been shown that a number of non‐small cell lung cancer (NSCLC) cell lines express high levels of CXCR4, which is associated with aggressive behavior, and that CXCL12‐activated CXCR4 promotes migration and invasion of these cell lines in vitro [11,13]

Summary

Introduction

Lung cancer ranks as the most frequent type of cancer in males worldwide with increasing incidence rates according to the epidemiology data [1]. Great advances have been achieved in chemotherapy and radiotherapy, only small, incremental improvements in the outcome of lung cancer have been realized, and the long‐term survival rate of lung cancer patients has not improved significantly. Metastatic spread to the regional lymph nodes, liver, bone and brain, which is characteristic of non‐small cell lung cancer (NSCLC), constitutes the primary source of morbidity and mortality in lung cancer. The majority of patients present with locally advanced (37%) or metastatic (38%) disease at the time of diagnosis [2,3]. Receptors may represent opportunistic targets for engineering vehicles that localize in primary and distal lung tumors

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