Expression of monocyte chemoattractant protein-1 and CC chemokine receptor 2 in non-small cell lung cancer and its significance

Abstract

Expression of monocyte chemoattractant protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2) and its significance has been demonstrated in some cancer cells in recent clinical studies. However, the role of tumor MCP-1 and CCR2 expression in non-small cell lung cancer (NSCLC) remains unknown. The aim of the present study was to investigate the prognostic significance of MCP-1 and CCR2 expression in NSCLC cells. The relationship between MCP-1 and CCR2 expression in NSCLC cancer cells was examined by immunohistochemical staining of surgical specimens from 134 patients. Sixty-five of these patients had follow-up records. Kaplan-Meier analysis and Cox regression model were used to assess overall survival according to the presence or absence of MCP-1 and CCR2 expression in tumor cells. MCP-1 was detected in cancer cells of 107 NSCLC (79.9 %) and CCR2 was detected in cancer cells of 39 NSCLC (29.1 %). MCP-1 expression was correlated with sex, smoking habits, histology, and tumor size. Presence of MCP-1 in tumor cells was associated with better overall survival (P = 0.018). By multivariate analysis, MCP-1 expression in cancer cells showed an independent prognostic factor for overall survival (P = 0.002, hazard ratio [HR] = 0.256, 95 % confidence interval [CI] = 0.106-0.616). There was no significant relationship between CCR2 expression in tumor cells and clinical and pathological characteristics. Also, no significant positive correlation between MCP-1 and CCR2 expression was revealed by Spearman correlation analysis. Our data indicate that MCP-1 is overexpressed in NSCLC cells. Its expression in cancer cells is associated with better survival in NSCLC patients.

High levels of CCL2 or CCL4 in the tumor microenvironment predict unfavorable survival in lung adenocarcinoma

“…Moreover, Zhang et al . reported that the presence of CCL2‐positive cancer cells was high in LUAD relative to LUSC and other histological types . A recent study demonstrated that Lewis lung carcinoma cells harbor the activating Kras G12C mutation, which upregulates CCL2 production linking cancer‐associated inflammation .…”

“…34 Moreover, Zhang et al reported that the presence of CCL2-positive cancer cells was high in LUAD relative to LUSC and other histological types. 35 A recent study demonstrated that Lewis lung carcinoma cells harbor the activating Kras G12C mutation, which upregulates CCL2 production linking cancer-associated inflammation. 36 A previous study reported that knockdown of CCL2 and CCL4 in lung cancer cells could suppress macrophage invasion under co-culture conditions.…”

Macrophage and Tumor Cell Cross-Talk Is Fundamental for Lung Tumor Progression: We Need to Talk

“…CCL2 binds to its receptor CCR2 to mediate its effect through an autocrine or paracrine manner (130). Expression of CCL2, CCR2 or in combination with IL6 and IL10 correlates with a worse prognosis in lung cancer patients (61,78,79). In various cancers, the crosstalk of TAMs with tumor cells via the CCL2/CCR2 axis play multiple roles in cancer development, such as monocyte/macrophage recruitment at the tumor site (131), tumor progression, EMT, invasion, and metastasis (132).…”

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

“…CCL2 is produced by endothelial cells and fibroblasts [12] and by a variety of activating cells, such as lymphocytes and macrophages [9]. Recent studies have reported that CCL2 is overexpressed in a majority of solid cancer types, including breast cancer, prostate cancer, esophageal carcinoma, colon cancer, pancreatic cancer, ovarian cancer [8, 13–17] and NSCLC [18]. …”

“…In patients with NSCLC, positive CCL2 expression was observed more frequently in men than in women, in never-smokers than in smokers, in adenocarcinoma than in other histological types, and in smaller tumors among the patients with NSCLC. However, there was no relationship of tumor CCR2 expression with gender, smoking habits, histologic type of tumor and tumor size [18, 24]. However, its roles in NSCLC development remain unclear.…”