CCL2 as an important mediator of prostate cancer growth in vivo through the regulation of macrophage infiltration.
The ability of CCL2 to influence prostate cancer tumorigenesis and metastasis may occur through two distinct mechanisms: 1) a direct effect on tumor cell growth and function, and 2) an indirect effect on the tumor microenvironment by the regulation of macrophage mobilization and infiltration into the tumor bed. We have previously demonstrated that CCL2 exerts a direct effect on prostate cancer epithelial cells by the regulation of their growth, invasion, and migration, resulting in enhanced tumorigenesis and metastasis. Here we describe an indirect effect of CCL2 on prostate cancer growth and metastasis by regulating monocyte/macrophage infiltration into the tumor microenvironment and by stimulating a phenotypic change within these immune cells to promote tumor growth (tumor-associated macrophages). VCaP prostate cancer cells were subcutaneously injected in male SCID mice and monitored for tumor volume, CD68(+) macrophage infiltration, and microvascular density. Systemic administration of anti-CCL2 neutralizing antibodies (CNTO888 and C1142) significantly retarded tumor growth and attenuated CD68(+) macrophage infiltration, which was accompanied by a significant decrease in microvascular density. These data suggest that CCL2 contributes to prostate cancer growth through the regulation of macrophage infiltration and enhanced angiogenesis within the tumor.
Loberg
Robert D
RD
Department of Urology, University of Michigan Urology Center, Ann Arbor, MI 48109-0946, USA. rloberg@umich.edu
Ying
Chi
C
Craig
Matt
M
Yan
Li
L
Snyder
Linda A
LA
Pienta
Kenneth J
KJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D018932:Chemokine CCL2
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