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Cancer Res. 2014 Dec 1;74(23):7103-14. doi: 10.1158/0008-5472.CAN-14-0612.

CCR5 receptor antagonists block metastasis to bone of v-Src oncogene-transformed metastatic prostate cancer cell lines.

Author information

1
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Faculty of Pharmacy, Nutrition, and Health Science, University of Calabria, Arcavacata di Rende, Italy.
2
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
3
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México.
4
Faculty of Pharmacy, Nutrition, and Health Science, University of Calabria, Arcavacata di Rende, Italy.
5
Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Department of Pharmacology and Physiology, Drexel University, Philadelphia, Pennsylvania.
6
Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania.
7
Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania.
8
Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania.
9
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. director@kimmelcancercenter.org.

Abstract

Src family kinases (SFK) integrate signal transduction for multiple receptors, regulating cellular proliferation, invasion, and metastasis in human cancer. Although Src is rarely mutated in human prostate cancer, SFK activity is increased in the majority of human prostate cancers. To determine the molecular mechanisms governing prostate cancer bone metastasis, FVB murine prostate epithelium was transduced with oncogenic v-Src. The prostate cancer cell lines metastasized in FVB mice to brain and bone. Gene expression profiling of the tumors identified activation of a CCR5 signaling module when the prostate epithelial cell lines were grown in vivo versus tissue cultures. The whole body, bone, and brain metastatic prostate cancer burden was reduced by oral CCR5 antagonist. Clinical trials of CCR5 inhibitors may warrant consideration in patients with CCR5 activation in their tumors.

PMID:
25452256
PMCID:
PMC4294544
DOI:
10.1158/0008-5472.CAN-14-0612
[Indexed for MEDLINE]
Free PMC Article

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