Effect of chemokine receptors CXCR4 and CCR7 on the metastatic behavior of human colorectal cancer

Purpose: The expression of chemokine receptors CXCR4 and CCR.7 has been associated with tumor dissemination and poor prognosis in a limited number of tumor entities. However, no data are currently available on the impact of chemokine receptor expression on disease progression and prognosis in human colorectal cancer. Experimental Design: The expression of CXCR4 and CCR7 was evaluated in 96 patients with histologically confirmed colorectal cancers and in four colorectal cancer cell lines by immunohistochemical staining. Furthermore, cell migration assays were done with SW480, SW620, and LS174T cancer cells to confirm the effect of the CXCR4 ligand stromal cell-derived factor 1alpha on migration. Results: Human colorectal cancer specimens and cell lines displayed a CXCR4 and CCR7 expression with variable intensities. Interestingly, strong expression of CXCR4, but not of CCR7, was significantly associated with higher Union International Contre Cancer stages 3/4 (P = 0.0017), lymph node metastasis (P = 0.00375), and distant metastasis (P = 0.00003) and further correlated with a reduced 3-year survival rate (P = 0.1). Strong CXCR4 and CCR7 expression positively correlated with the location of the primary tumor in the rectum (P < 0.01). Furthermore, activation of CXCR4-expressing cancer cells by stromal cell-derived factor 1alpha resulted in a significant increase of cell migration (P < 0.014). Conclusion: Strong expression of CXCR4 by colorectal cancer cells is significantly associated with lymphatic and distant dissemination in patients with colorectal cancer as well as with cancer cell migration in vitro.