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In Reply

Department of Hematology and Oncology, Charité, Campus Benjamin Franklin, Berlin, Germany

We appreciate the comments from Dr Rubie et al¹ on our recent article describing the association between chemokine receptor (CCR6) expression level in primary colon cancer and synchronous liver metastasis.² The mechanism of CCR6-mediated promotion of liver metastasis is yet unclear. Based on various animal studies, the most evident mechanism is the selective expression of chemokines in certain tissues leading to promotion of metastasis by attracting specific CCR-expressing tumor cells.^3,4 Supporting this concept, a constitutive expression of the CCR6-ligand (CCL) 20 was described in the portal fields of the liver,⁵ the presumed entry site of colorectal cancer cells reaching the liver through the portal vein. The study by Rubie et al confirmed an increased expression of the CCR6 ligand CCL20 in the liver as compared with other organs. However, the finding by Rubie et al of higher levels of CCL20 in the normal liver tissue surrounding colorectal cancer metastasis as compared with liver tissue from nontumor patients is very interesting and points towards an additional mechanism. The tumor itself may be able to induce CCL20 production in surrounding liver tissue providing support for tumor growth in a paracrine fashion. Further, chemokines can also contribute to the progression of cancer in an autocrine fashion⁶ and colon cancer cells were shown to express constitutively CCL20.⁷ In summary, we fully agree with Rubie et al that the characterization of the underlying mechanisms for promotion of colorectal cancer liver metastasis by CCR6/CCL20 is of great relevance as targeting of these molecules may represent novel treatment strategies.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Rubie C, Oliveira V, Kempf K, et al: Involvement of chemokine receptor CCR6 in colorectal cancer metastasis. Tumor Biol 27 : 166 -174, 2006[CrossRef]

2. Ghadjar P, Coupland SE, Na IK, et al: Chemokine receptor CCR6 expression level and liver metastases in colorectal cancer. J Clin Oncol 24 : 1910 -1916, 2006[Abstract/Free Full Text]

3. Müller A, Homey B, Soto H, et al: Involvement of chemokine receptors in breast cancer metastasis. Nature 410 : 50 -56, 2001[CrossRef][Medline]

4. Wiley HE, Gonzalez EB, Maki W, et al: Expression of CC chemokine receptor-7 and regional lymph node metastasis of B16 murine melanoma. J Natl Cancer Inst 93 : 1638 -1643, 2001[Abstract/Free Full Text]

5. Shimizu Y, Murata H, Kashii Y, et al: CC-chemokine receptor 6 and its ligand macrophage inflammatory protein 3 alpha might be involved in the amplification of local necroinflammatory response in the liver. Hepatology 34 : 311 -319, 2001[CrossRef][Medline]

6. Wang B, Hendricks DT, Wamunyokoli F, et al: A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer. Cancer Res 66 : 3071 -3077, 2006[Abstract/Free Full Text]

7. Yang CC, Ogawa H, Dwinell MB, et al: Chemokine receptor CCR6 transduces signals that activate p130Cas and alter cAMP-stimulated ion transport in human intestinal epithelial cells. Am J Physiol Cell 288 : 321 -328, 2005

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Related Correspondence

• Chemokine Receptor CCR6 Expression in Colorectal Liver Metastasis
  Claudia Rubie, Vilma Oliveira-Frick, Bettina Rau, Martin Schilling, and Mathias Wagner
  JCO 2006 24: 5173-5174 [Full Text]

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