This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schimanski, C. C. Articles by Moehler, M. Search for Related Content PubMed PubMed Citation Articles by Schimanski, C. C. Articles by Moehler, M.

Effect of Chemokine Receptors CXCR4 and CCR7 on the Metastatic Behavior of Human Colorectal Cancer

¹ First Department of Internal Medicine and Institutes of ² Pathology and ³ Surgery, Johannes Gutenberg University of Mainz, Mainz, Germany and ⁴ Unit of Toxicology and Chemotherapy, German Cancer Research Centre, Heidelberg, Germany

Requests for reprints: Carl C. Schimanski, First Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. Phone: 49-6131-177276; Fax: 49-6131-177276; E-mail: dr_schimanski{at}yahoo.de.

Purpose: The expression of chemokine receptors CXCR4 and CCR7 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 1 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 1 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.

Key Words: lymph node metastases • liver metastases • dissemination

This article has been cited by other articles:

				J. Meijer, J. Ogink, B. Kreike, D. Nuyten, K. E. de Visser, and E. Roos The Chemokine Receptor CXCR6 and Its Ligand CXCL16 Are Expressed in Carcinomas and Inhibit Proliferation Cancer Res., June 15, 2008; 68(12): 4701 - 4708. [Abstract] [Full Text] [PDF]

				S. K. Lau, P. C. Boutros, M. Pintilie, F. H. Blackhall, C.-Q. Zhu, D. Strumpf, M. R. Johnston, G. Darling, S. Keshavjee, T. K. Waddell, et al. Three-Gene Prognostic Classifier for Early-Stage Non Small-Cell Lung Cancer J. Clin. Oncol., December 10, 2007; 25(35): 5562 - 5569. [Abstract] [Full Text] [PDF]

				E. J. Cheadle, K. Riyad, D. Subar, D. G. Rothwell, G. Ashton, H. Batha, D. J. Sherlock, R. E. Hawkins, and D. E. Gilham Eotaxin-2 and Colorectal Cancer: A Potential Target for Immune Therapy Clin. Cancer Res., October 1, 2007; 13(19): 5719 - 5728. [Abstract] [Full Text] [PDF]

				N Cabioglu, Y Gong, R Islam, K. Broglio, N Sneige, A Sahin, A. Gonzalez-Angulo, P Morandi, C Bucana, G. Hortobagyi, et al. Expression of growth factor and chemokine receptors: new insights in the biology of inflammatory breast cancer Ann. Onc., June 1, 2007; 18(6): 1021 - 1029. [Abstract] [Full Text] [PDF]

				S. Hojo, K. Koizumi, K. Tsuneyama, Y. Arita, Z. Cui, K. Shinohara, T. Minami, I. Hashimoto, T. Nakayama, H. Sakurai, et al. High-Level Expression of Chemokine CXCL16 by Tumor Cells Correlates with a Good Prognosis and Increased Tumor-Infiltrating Lymphocytes in Colorectal Cancer Cancer Res., May 15, 2007; 67(10): 4725 - 4731. [Abstract] [Full Text] [PDF]

				I. Kryczek, S. Wei, E. Keller, R. Liu, and W. Zou Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis Am J Physiol Cell Physiol, March 1, 2007; 292(3): C987 - C995. [Abstract] [Full Text] [PDF]

				J Kodama, Hasengaowa, T Kusumoto, N Seki, T Matsuo, Y Ojima, K Nakamura, A Hongo, and Y Hiramatsu Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer Ann. Onc., January 1, 2007; 18(1): 70 - 76. [Abstract] [Full Text] [PDF]

				A. Ottaiano, R. Franco, A. Aiello Talamanca, G. Liguori, F. Tatangelo, P. Delrio, G. Nasti, E. Barletta, G. Facchini, B. Daniele, et al. Overexpression of Both CXC Chemokine Receptor 4 and Vascular Endothelial Growth Factor Proteins Predicts Early Distant Relapse in Stage II-III Colorectal Cancer Patients. Clin. Cancer Res., May 1, 2006; 12(9): 2795 - 2803. [Abstract] [Full Text] [PDF]

				P. Ghadjar, S. E. Coupland, I.-K. Na, M. Noutsias, A. Letsch, A. Stroux, S. Bauer, H. J. Buhr, E. Thiel, C. Scheibenbogen, et al. Chemokine Receptor CCR6 Expression Level and Liver Metastases in Colorectal Cancer J. Clin. Oncol., April 20, 2006; 24(12): 1910 - 1916. [Abstract] [Full Text] [PDF]

				R. A. Bartolome, I. Molina-Ortiz, R. Samaniego, P. Sanchez-Mateos, X. R. Bustelo, and J. Teixido Activation of Vav/Rho GTPase Signaling by CXCL12 Controls Membrane-Type Matrix Metalloproteinase-Dependent Melanoma Cell Invasion Cancer Res., January 1, 2006; 66(1): 248 - 258. [Abstract] [Full Text] [PDF]

				I. Airoldi, L. Raffaghello, E. Piovan, C. Cocco, B. Carlini, A. Amadori, M. V. Corrias, and V. Pistoia CXCL12 Does Not Attract CXCR4+ Human Metastatic Neuroblastoma Cells: Clinical Implications Clin. Cancer Res., January 1, 2006; 12(1): 77 - 82. [Abstract] [Full Text] [PDF]