Abstract
The link between inflammation and colorectal carcinoma has been acknowledged. However, the impact of bacterial lipopolysaccharide (LPS) binding to Toll-like receptor 4 (TLR4) on chemokine receptors in human colorectal carcinoma cells still remains to be elucidated. The present study shows that exposure to LPS elevated CXC chemokine receptor 7 (CXCR7) expression in colorectal carcinoma SW480 and Colo 205 cell lines expressing TLR4/myeloid differential protein (MD-2). CXCR7 is associated with SW480 cell proliferation and migration. However, exposure of SW480 and Colo 205 cells to LPS had no effect on CXCR4 expression. To further support the above results, the expression of TLR4, MD-2, and CXCR7 was analyzed in human colorectal carcinoma tissues. Higher rates of TLR4 (53%), MD-2 (70%), and CXCR7 (29%) expression were found in colorectal carcinoma tissues than in normal tissues. We demonstrated that the recombination of TLR4, MD-2 and CXCR7 strongly correlated with tumor size, lymph node metastasis and distant metastasis in colorectal carcinoma tissue samples (p = 0.037, p = 0.002, p = 0.042, resp.). Accordingly, simultaneous examination of the expression of TLR4, MD-2 and CXCR7 in cancer tissues of colorectal carcinoma may provide valuable prognostic diagnosis of carcinoma growth and metastasis. Interplay of TLR4, MD-2 and CXCR7 may be of interest in the context of novel immunomodulatory therapies for colorectal carcinoma.
Highlights
Colorectal carcinoma is one of the most common cancers, which accounts for almost half a million deaths annually worldwide
Exposure of Toll-like receptor 4 (TLR4) to LPS elevates CXC chemokine receptor 7 (CXCR7) expression in colorectal carcinoma SW480 and Colo 205 cell lines mRNA of colorectal carcinoma cell lines encoding TLR4 with its co-molecules, MD-2 were determined using Reverse transcriptase (RT)-PCR
The analysis of RT-PCR products showed that TLR4 and MD-2 were constitutively expressed in 4 out of 8 human colorectal carcinoma cell lines, including Colo 205, RKO, SW480 and SW620, whereas TLR4 and MD-2 were present respectively in only two cell lines such as DLD-1 and HCT-29 (Fig. 1A)
Summary
Colorectal carcinoma is one of the most common cancers, which accounts for almost half a million deaths annually worldwide. Death of these patients results from uncontrolled metastatic disease, including liver, lymph nodes, or peritoneum metastases. Inflammation is considered a risk factor for many common malignancies including cancers of the lung [1], breast [2], and colorectum [3]. Chronic inflammatory bowel disease (IBD) such as chronic ulcerative colitis and Crohn’s disease is associated with increased incidence of colorectal carcinoma as compared with the normal population [4,5]. The link between inflammation and colorectal carcinoma offers the possibility of identifying novel ways to prevent cancer. The molecular mechanisms whereby chronic inflammation predisposes to cancer remain elusive
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