title: CCR5 receptor antagonists block metastasis to bone of v-Src oncogene-transformed metastatic prostate cancer cell lines.
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.
authors.affiliation: 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.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sicoli
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Xuanmao
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ju
authors.affiliation: 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.
authors.forename: Marco
authors.initials: M
authors.lastname: Velasco-Velazquez
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Adam
authors.initials: A
authors.lastname: Ertel
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Sankar
authors.initials: S
authors.lastname: Addya
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.affiliation: Faculty of Pharmacy, Nutrition, and Health Science, University of Calabria, Arcavacata di Rende, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Andò
authors.affiliation: Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Department of Pharmacology and Physiology, Drexel University, Philadelphia, Pennsylvania.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Fatatis
authors.affiliation: Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Bishnuhari
authors.initials: B
authors.lastname: Paudyal
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.affiliation: Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Mathew L
authors.initials: ML
authors.lastname: Thakur
authors.affiliation: Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.affiliation: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. director@kimmelcancercenter.org.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D001932:Brain Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary; D065100:CCR5 Receptor Antagonists / Q000494:pharmacology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D016391:Genes, src; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D065100:CCR5 Receptor Antagonists; C584933:CCR5 protein, human; D047428:Protein Kinase Inhibitors; D019713:Receptors, CCR5; D019061:src-Family Kinases