Oncotarget

Research Papers:

Targeting CCR2 with its antagonist suppresses viability, motility and invasion by downregulating MMP-9 expression in non-small cell lung cancer cells

Jun An, Ying Xue, Meijun Long, Ge Zhang, Junhang Zhang _ and Hang Su

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Oncotarget. 2017; 8:39230-39240. https://doi.org/10.18632/oncotarget.16837

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Abstract

Jun An1,*, Ying Xue2,*, Meijun Long3,*, Ge Zhang2, Junhang Zhang1 and Hang Su4

1Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China

2Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China

3Breast Cancer Center and Department of Thyroid and Breast Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China

4Department of Radiation Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA

*These authors have contributed equally to this work

Correspondence to:

Junhang Zhang, email: zhangjh33@mail.sysu.edu.cn

Hang Su, email: suh3@uthscsa.edu

Keywords: CCR2 antagonist, MMP-9, non-small cell lung cancer, viability, motility and invasion

Received: September 23, 2016     Accepted: March 09, 2017     Published: April 05, 2017

ABSTRACT

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which is the leading cancer killer in the world. Despite the recent advances in its diagnosis and therapy, the prognosis of NSCLC patients remains very poor, mainly due to the development of drug resistance and metastasis. Both the chemokine network and the matrix metalloproteinase (MMP) system play important roles in cancer cell metastasis. The disruption of CCL2/CCR2 chemokine signaling has been shown to suppress cancer cellviability and metastasis. CCL2-neutralizing antibodies, which have shown promising therapeutic efficacy in several cancer models, are not widely used due to technical issues. CCR2 antagonism has thus become an alternative method for cancer treatment. However, the effect of CCR2 antagonists on NSCLC progression remains poorly understood. Here, we investigated the effect of CCR2 antagonist (CAS445479-97-0) on the proliferation, migration and invasion of human lung adenocarcinoma A549 cells by using WST-1 cell viability assay, transwell migration assay, wound healing scratch assay and Matrigel invasion assay. We demonstrated that CCL2 treatment promoted A549 cell viability, motility and invasion by upregulating MMP-9 expression and that this induction was significantly suppressed by CAS 445479-97-0. Taken together, our data suggested that the CCR2 antagonist would be a potential drug for treating CCR2-positive NSCLC patients.


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