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.
Highlights
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which is the leading cancer killer in the world [1, 2]
We demonstrated that CCL2 treatment promoted A549 cell viability, motility and invasion by upregulating matrix metalloproteinase (MMP)-9 expression and that this induction was significantly suppressed by CAS 445479-97-0
The current study investigated the anti-proliferative, antimotile and anti-invasive activities of an antagonist against Chemokine Receptor 2 (CCR2), CAS 445479-97-0, by blocking the CCL2/CCR2 axis interaction and downregulating MMP-9 protein expression in human lung adenocarcinoma A549 cells in vitro
Summary
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which is the leading cancer killer in the world [1, 2]. NSCLC patients can be generally classified into three stages: early (non-metastatic), locally advanced (confined to the thoracic cavity) and distant metastasis (outside of the thoracic cavity). The prognosis of NSCLC patients remains very poor, despite the recent advances in therapy, probably due to the development of locally advanced or metastatic disease at the time of diagnosis [3]. The main therapeutic strategies for advanced and metastatic NSCLC are chemotherapy and specific mutagenic inhibitors for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-met and Kras [4]. Specific mutagenic inhibitors are only suitable for the rare mutagenic cases [5], and most cases of NSCLC rapidly develop acquired resistance to www.impactjournals.com/oncotarget chemotherapy [6]. There is an urgent need for new therapeutic approaches for NSCLC patients
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