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. 2011;6(12):e27399.
doi: 10.1371/journal.pone.0027399. Epub 2011 Dec 13.

Alteration of CXCR7 expression mediated by TLR4 promotes tumor cell proliferation and migration in human colorectal carcinoma

Huanbai Xu  1 , Qiong Wu, Shipeng Dang, Min Jin, Jingwei Xu, Yiji Cheng, Minglin Pan, Yugang Wu, Chunhui Zhang, Yanyun Zhang
Affiliations

Alteration of CXCR7 expression mediated by TLR4 promotes tumor cell proliferation and migration in human colorectal carcinoma

Huanbai Xu et al. PLoS One. 2011.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. LPS-TLR4-MD-2 induced CXCR7 expression alteration in colorectal carcinoma cell line.
A, Reverse transcriptase (RT)-PCR analysis (TLR4 and MD-2) on RNA isolated from 8 human colorectal carcinoma cell lines. B, LPS induced time- and dose-dependent CXCR7 and CXCR4 protein expression alterations. SW480 and Colo 205 cell lines were incubated with LPS (500 ng/ml) in the presence or absence of PMB (500 µg/ml), representative flow cytometric analysis of CXCR7 expression alterations were showed. C, LPS exposure induced a significant CXCR7 expression increase in total RNA conten. D, Exposure of SW480 and Colo 205 cell lines to LPS (500 ng/ml) had no effect on CXCR4 expression.
Figure 2
Figure 2. Knockdown effect of MD-2 on exposure of TLR4 to LPS in SW480 and Colo 205 cell lines.
A, SW480 and Colo 205 cell lines were transfected transiently with siRNA or negative control sequence(NC). SW480 and Colo 205 cell lines transfected with the MD-2 siRNA sequence exhibited a marked reduction in MD-2 mRNA and protein level compared with NC. B, After LPS treatment, flow cytometry and real-time quantitative-PCR were performed. Knockdown of MD-2 inhibited LPS-mediated CXCR7 expression.
Figure 3
Figure 3. Proliferation, apoptosis and migration of CXCR7-positive SW480 and Colo 205 cell lines incubated with LPS.
A, Incubation with LPS, SW480 cell line pretreated with AMD3100 (10 µg/ml) proliferated significantly in response to CXCL12 (100 ng/ml; 48 h), Colo 205 cell line also proliferated significantly in response to CXCL12. B, CXCL12 activation of its receptor CXCR7 did not exert an antiapoptotic effect. C, Pretreatment with AMD3100, SW480 cell line migrated significantly more in response to CXCL12 after 24 h of incubation with LPS, Colo 205 cell line also migrated significantly in response to CXCL12.
Figure 4
Figure 4. Representative examples of immunohistochemical staining of TLR4, MD-2, and CXCR7 in colorectal carcinoma tissues (original magnification 100×).
Positive staining was observed as a dark brown color. Normal colorectal tissues showed negative immunohistochemical staining of TLR4 (A), MD-2 (B), and CXCR7 (C), and colorectal carcinoma tissues showed strong staining of TLR4 (D), MD-2 (E), and CXCR7 (F).
See this image and copyright information in PMC

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