Duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth

The Duffy antigen/receptor for chemokines (DARC) is a promiscuous chemokine receptor that binds to members of the CXC chemokine family possessing angiogenic properties. The DARC is expressed on erythrocytes and endothelial cells and is required for Plasmodium vivax infection of erythrocytes. Approxi...

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Bibliographic Details
Published in:The FASEB journal 2006, Vol.20 (1), p.59-64
Main Authors: Shen, Hui, Schuster, Rebecca, Stringer, Keith F, Waltz, Susan E, Lentsch, Alex B
Format: Article
Language:English
Subjects:
Adenocarcinoma - metabolism
African‐American
angiogenesis
Animals
Blood Group Antigens - genetics
Blood Group Antigens - metabolism
cancer
Cell Line
Cell Proliferation
Chemokines - metabolism
Duffy Blood-Group System
endothelial cell
Erythrocytes - metabolism
Gene Deletion
Gene Expression Regulation, Neoplastic
Male
Mice
Mice, Transgenic
Plasmodium vivax
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
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Summary:The Duffy antigen/receptor for chemokines (DARC) is a promiscuous chemokine receptor that binds to members of the CXC chemokine family possessing angiogenic properties. The DARC is expressed on erythrocytes and endothelial cells and is required for Plasmodium vivax infection of erythrocytes. Approximately 70% of African-Americans lack erythrocyte expression of the DARC as a genetic mechanism of protection against malaria infection. African-American men have a 60% greater incidence of prostate cancer and a 2-fold higher mortality rate than Caucasian men. Using a transgenic model of prostate cancer with DARC-deficient mice, we tested the hypothesis that lack of DARC expression on erythrocytes contributes to enhanced prostate tumor growth. In vitro, erythrocytes from wild-type mice but not DARC-deficient mice cleared angiogenic chemokines produced by prostate cancer cells and reduced endothelial cell chemotaxis. In vivo, tumors from DARC-deficient mice had higher intra-tumor concentrations of angiogenic chemokines, increased tumor vessel density, and greatly augmented prostate tumor growth. The data suggest that the DARC functions to clear angiogenic CXC chemokines from the prostate tumor microcirculation and that the lack of erythroid DARC, as occurs in the majority of African-Americans, may be a contributing factor to the increased mortality to prostate cancer in this population.--Shen, H., Schuster, R., Stringer, K. F., Waltz, S. E., Lentsch, A. B. The Duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.05-4764com