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Critical and opposing roles of the chemokine receptors CXCR2 and CXCR3 in prostate tumor growth
Author(s) -
Shen Hui,
Schuster Rebecca,
Lu Bao,
Waltz Susan E.,
Lentsch Alex B.
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20476
Subject(s) - cxc chemokine receptors , cxcr3 , chemokine receptor , prostate , receptor , medicine , chemokine , biology , cancer
Background Angiogenic and angiostatic CXC chemokines mediate their effects via the receptors, CXCR2 and CXCR3, respectively. The current study sought to determine whether the presence of these receptors alters prostate tumor growth. Methods Endothelial cell chemotaxis of prostate cell‐derived products was determined in vitro. Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice was bred with CXCR2‐ or CXCR3‐knockout mice to determine the effects of these genes on prostate tumor growth. Results Normal prostate epithelial cells release CXCR3 ligands that limit endothelial cell chemotaxis. Prostate cancer cells release CXCR2 ligands that stimulated endothelial cell chemotaxis. Tumors in TRAMP/CXCR2 −/− mice were significantly smaller than those in TRAMP/CXCR2 +/+ mice and had reduced angiogenesis. In contrast, tumors in TRAMP/CXCR3 −/− mice were palpable much earlier than TRAMP/CXCR3 +/+ mice and had greatly increased angiogenesis. Conclusions The data suggest that signaling through CXCR2 and CXCR3 represents important counter‐regulatory mechanisms that control the growth of prostate tumors. Prostate © 2006 Wiley‐Liss, Inc.