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

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 m...

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Podrobná bibliografia
Vydané v:	Cancer research (Chicago, Ill.) Ročník 74; číslo 23; s. 7103
Hlavní autori:	Sicoli, Daniela, Jiao, Xuanmao, Ju, Xiaoming, Velasco-Velazquez, Marco, Ertel, Adam, Addya, Sankar, Li, Zhiping, Andò, Sebastiano, Fatatis, Alessandro, Paudyal, Bishnuhari, Cristofanilli, Massimo, Thakur, Mathew L, Lisanti, Michael P, Pestell, Richard G
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.12.2014
Predmet:	Animals Bone Neoplasms - metabolism Bone Neoplasms - prevention & control Bone Neoplasms - secondary Brain Neoplasms - metabolism Brain Neoplasms - prevention & control Brain Neoplasms - secondary CCR5 Receptor Antagonists - pharmacology Cell Line, Transformed Cell Line, Tumor Epithelial Cells - drug effects Epithelial Cells - metabolism Epithelial Cells - pathology Epithelium - drug effects Epithelium - metabolism Epithelium - pathology Gene Expression Profiling - methods Genes, src Humans Male Mice Prostatic Neoplasms - drug therapy Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Protein Kinase Inhibitors - pharmacology Receptors, CCR5 - genetics Receptors, CCR5 - metabolism src-Family Kinases - genetics src-Family Kinases - metabolism
ISSN:	1538-7445, 1538-7445
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1538-7445 1538-7445
DOI:	10.1158/0008-5472.CAN-14-0612