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

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.

CCL2/CCR2 axis induces hepatocellular carcinoma invasion and epithelial-mesenchymal transition in�vitro through activation of the Hedgehog pathway

“…1B , CCL2 time-dependently stimulated MHCC97H proliferation, indicating that CCL2 could effectively stimulate MHCC97H proliferation. These findings were consistent with the results that CCL2 promoted non-small cell lung cancer A549 cell viability ( 20 ). The MHCC97H cells were treated with or without CCL2 for 24 h and then the invasion ability was assessed via a Transwell assay.…”

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

“…For this reason, inactivation of the CCL2/MCP-1→CCR2 axis by using anti-CCL2 antibodies or CCR2 antagonists increases the effectiveness of immunotherapy [247,248]. This therapeutic approach also shows anticancer properties in monotherapy [249][250][251][252][253][254]. Similarly, because of a significant pro-cancer effect, it is postulated that treatment may target the functioning of CCL3/MIP-1α [19,255], CCL5/RANTES [45,256].…”

Serum amyloid a, a potential biomarker both in serum and tissue, correlates with ovarian cancer progression

“…4b-d). O'Hara R, and Tamamoto T et al had reported that SAA was involved in adhesion, migration, and tissue in ltration of in ammatory cells, induced matrix metalloproteinases which could interact with degrading extracellular matrix (ECM) controlling the diffusion and migration of cells [25][26][27][28][29][30]. Possible mechanisms of SAA for stimulating MMP-9 might be via formyl peptide receptor like-1-mediated signaling [31].…”