Alteration of CXCR7 Expression Mediated by TLR4 Promotes Tumor Cell Proliferation and Migration in Human Colorectal Carcinoma

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.

Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma

“…40 IHC staining was independently examined by two clinical pathologists who were unaware of the patient outcome. Interpretation and evaluation of IHC results was as described previously.…”

“…Interpretation and evaluation of IHC results was as described previously. 40 Cell migration assay Twenty four-well transwell insert chambers (Merck KgaA, Darmstadt, Germany) were used for cell migration assy. One lakh cells (serum-starved overnight and then treated with or without GW9508 for 72 h before the assay) were added to the top chambers in serum-free medium (200 ml), and the bottom chambers were filled with medium containing 10% FBS.…”

Plasmacytoid Dendritic Cells Play a Key Role in Tumor Progression in Lipopolysaccharide-Stimulated Lung Tumor–Bearing Mice

“…Since then, numerous studies have been conducted to investigate the effects of LPS on tumors. Several studies on tumor cell lines showed that TLR4 stimulation facilitates cell proliferation (4,5). Similarly, LPS facilitates carcinogenesis in mouse models of skin cancer (6), lung cancer (7), breast cancer (8), and colon cancer (9).…”

CXCR4–CXCL12–CXCR7, TLR2–TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients

“…LPS-induced inflammation activates TLR4 that in turn induces CXCR4 and/or CXCR7 expression in tumor cells, enhancing the response to CXCL12 to promote invasion and cell dissemination. 19 LPS exposure induced CXCR7 expression in human colon cancer cell lines SW480 and Colo 205 expressing TLR4/myeloid differential protein (MD-2). 19 Moreover, N15P polypeptide, a new CXCR4 antagonist derived from the Kaposi sarcoma secreted cytokine vMIP-II reversed the LPS-induced inflammation in human PBMC.…”

“…19 LPS exposure induced CXCR7 expression in human colon cancer cell lines SW480 and Colo 205 expressing TLR4/myeloid differential protein (MD-2). 19 Moreover, N15P polypeptide, a new CXCR4 antagonist derived from the Kaposi sarcoma secreted cytokine vMIP-II reversed the LPS-induced inflammation in human PBMC. 20,21 Targeting PD-1 T-cell coreceptor and its ligand B7-H1/ PD-L1 induce durable tumor responses 22 nevertheless only a minority of patients respond, and it has been unclear which patients and which tumors are the best candidates for this therapy.…”