Title

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

Authors

Daniela Sicoli, Department of Cancer Biology; Sidney Kimmel Cancer Center, Thomas Jefferson University; Faculty of Pharmacy, Nutrition, and Health Science, University of Calabria
Xuanmao Jiao, Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Xiaoming Ju, Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Marco Velasco-Velazquez, Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University; Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México
Adam Ertel, Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson UniversityFollow
Sankar Addya, Kimmel Cancer Center, Department of Cancer Biology, Jefferson Medical College, Thomas Jefferson UniversityFollow
Z Li, Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Sebastiano Andò, Faculty of Pharmacy, Nutrition, and Health Science, University of Calabria
Alessandro Fatatis, Sidney Kimmel Cancer Center, Thomas Jefferson University; Department of Pharmacology and Physiology, Drexel University
Bishnuhari Paudyal, Department of Radiology, Thomas Jefferson UniversityFollow
Massimo Cristofanilli, Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Mathew L. Thakur, Department of Radiology, Sidney Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Michael P. Lisanti, Stem Cell Biology and Regenerative Medicine, Sidney Kimmel Cancer Center, Thomas Jefferson University; Manchester Centre for Cellular Metabolism, Breakthrough Breast Cancer Research Unit, University of ManchesterFollow
Richard Pestell, Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

12-1-2014

Comments

This article has been peer reviewed. It was published in: Cancer Research.

Volume 74, Issue 23, 1 December 2014, Pages 7103-7114.

The published version is available at DOI: 10.1158/0008-5472.CAN-14-0612

Copyright © 2014 American Association for Cancer Research

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.