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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| Published in: | Cancer research (Chicago, Ill.) Vol. 74; no. 23; p. 7103 |
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| Main Authors: | , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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United States
01.12.2014
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| ISSN: | 1538-7445, 1538-7445 |
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| 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. |
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| AbstractList | 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. 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.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. |
| Author | Thakur, Mathew L Pestell, Richard G Ju, Xiaoming Andò, Sebastiano Paudyal, Bishnuhari Lisanti, Michael P Jiao, Xuanmao Fatatis, Alessandro Li, Zhiping Sicoli, Daniela Addya, Sankar Ertel, Adam Velasco-Velazquez, Marco Cristofanilli, Massimo |
| Author_xml | – sequence: 1 givenname: Daniela surname: Sicoli fullname: Sicoli, Daniela organization: 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 – sequence: 2 givenname: Xuanmao surname: Jiao fullname: Jiao, Xuanmao organization: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania – sequence: 3 givenname: Xiaoming surname: Ju fullname: Ju, Xiaoming organization: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania – sequence: 4 givenname: Marco surname: Velasco-Velazquez fullname: Velasco-Velazquez, Marco organization: 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 – sequence: 5 givenname: Adam surname: Ertel fullname: Ertel, Adam organization: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania – sequence: 6 givenname: Sankar surname: Addya fullname: Addya, Sankar organization: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania – sequence: 7 givenname: Zhiping surname: Li fullname: Li, Zhiping organization: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania – sequence: 8 givenname: Sebastiano surname: Andò fullname: Andò, Sebastiano organization: Faculty of Pharmacy, Nutrition, and Health Science, University of Calabria, Arcavacata di Rende, Italy – sequence: 9 givenname: Alessandro surname: Fatatis fullname: Fatatis, Alessandro organization: Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Department of Pharmacology and Physiology, Drexel University, Philadelphia, Pennsylvania – sequence: 10 givenname: Bishnuhari surname: Paudyal fullname: Paudyal, Bishnuhari organization: Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania – sequence: 11 givenname: Massimo surname: Cristofanilli fullname: Cristofanilli, Massimo organization: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania – sequence: 12 givenname: Mathew L surname: Thakur fullname: Thakur, Mathew L organization: Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Department of Radiology, Thomas Jefferson University, Philadelphia, Pennsylvania – sequence: 13 givenname: Michael P surname: Lisanti fullname: Lisanti, Michael P organization: Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania – sequence: 14 givenname: Richard G surname: Pestell fullname: Pestell, Richard G email: director@kimmelcancercenter.org organization: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania. Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. director@kimmelcancercenter.org |
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| SubjectTerms | 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 |
| Title | CCR5 receptor antagonists block metastasis to bone of v-Src oncogene-transformed metastatic prostate cancer cell lines |
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