This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Horton, L. W. Articles by Richmond, A. Search for Related Content PubMed PubMed Citation Articles by Horton, L. W. Articles by Richmond, A.

Opposing Roles of Murine Duffy Antigen Receptor for Chemokine and Murine CXC Chemokine Receptor-2 Receptors in Murine Melanoma Tumor Growth

¹ Department of Veteran Affairs; ² Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee and ³ Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia

Requests for reprints: Ann Richmond, Department of Cancer Biology, Vanderbilt University School of Medicine, 2220 Pierce Avenue, 771 PRB, Nashville, TN 37232. Phone: 615-343-7777; Fax: 615-343-4539; E-mail: ann.richmond{at}vanderbilt.edu.

The Duffy antigen receptor for chemokines (DARC) has been classified as a "silent" receptor, as it can bind CXC and CC chemokines to undergo ligand-induced receptor internalization, but is not coupled to trimeric G proteins required for the classic G protein–coupled receptor–mediated signaling. CXC chemokine receptor-2 (CXCR2) has been shown to play a major role in tumor angiogenesis. To test the hypothesis that these two chemokine receptors might play opposing roles in the growth of melanoma tumors, we developed a transgenic mouse model, where the preproendothelin promoter/enhancer (PPEP) is used to drive expression of either murine DARC (mDARC) or murine CXCR2 (mCXCR2) in endothelial cells. We show herein that the growth of melanoma tumor xenografts, established from s.c. injection of immortalized murine melanocytes overexpressing macrophage inflammatory protein-2, was inhibited or enhanced in the PPEP-mDARC and PPEP-mCXCR2 transgenic mice, respectively, compared with control mice. The early tumors formed in mDARC transgenic mice exhibited a significantly higher number of infiltrating leukocytes compared with either the control or mCXCR2 transgenic mice, suggesting a potential role for DARC expressed on endothelial cells in leukocyte migration. In addition, the tumor-associated angiogenesis in mDARC transgenic mice was reduced when compared with the control. Conversely, tumor angiogenesis was significantly increased in mCXCR2 transgenic mice. Results indicate that endothelial cell overexpression of mDARC increased leukocyte trafficking to the tumor, reduced the growth of blood vessels into the tumor, and reduced the growth rate of the tumor, whereas endothelial cell overexpression of mCXCR2 had the reverse effect on tumor angiogenesis and growth. [Cancer Res 2007;67(20):9791–9]

This article has been cited by other articles:

				B. E. G. Rothberg, M. B. Bracken, and D. L. Rimm Tissue Biomarkers for Prognosis in Cutaneous Melanoma: A Systematic Review and Meta-analysis J Natl Cancer Inst, April 1, 2009; 101(7): 452 - 474. [Abstract] [Full Text] [PDF]