Source:http://linkedlifedata.com/resource/pubmed/id/18316587
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2008-3-4
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| pubmed:abstractText |
Approximately 30% of patients with renal cell carcinoma (RCC) develop bone metastasis, which is characterized by extensive osteolysis leading to severe bone pain and pathologic fracture. Although the mechanism of RCC-induced osteolysis is unknown, studies of bone metastasis have shown that tumor-induced changes in bone remodeling are likely mediated by alterations in the bone microenvironment. Here, we report the discovery of a novel osteoclast stimulatory factor secreted by RCC bone metastasis (RBM). Through microarray analysis, we found expression of the chemokine, macrophage inflammatory protein-1 delta (MIP-1 delta), to be increased in RBM versus patient-matched primary RCC tissues and confirmed this finding by quantitative reverse transcription-PCR (qRT-PCR) and ELISA (P < 0.05). Furthermore, MIP-1 delta expression in RBM tissues was significantly (P < 0.001) higher than in human bone marrow, suggesting a potential alteration of the bone microenvironment. The receptors for MIP-1 delta, CCR1 and CCR3, were expressed in both osteoclast precursors and mature, bone-resorbing osteoclasts as shown by qRT-PCR and Western analysis. In functional studies, MIP-1 delta stimulated chemotaxis of two osteoclast precursor cell types: murine bone marrow mononuclear cells (BM-MNC) and RAW 264.7 cells. Furthermore, MIP-1 delta treatment of murine calvaria caused increased bone resorption as determined by measurement of released calcium. Correspondingly, MIP-1 delta significantly enhanced osteoclast formation and activity in response to RANKL in both BM-MNC and RAW 264.7 cells. Taken together, these data suggest that MIP-1 delta expression is increased in RBM relative to RCC and bone marrow, and may promote RBM-induced osteolysis by stimulating the recruitment and differentiation of osteoclast precursors into mature osteoclasts.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
1538-7445
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
68
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1261-6
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| pubmed:meshHeading |
pubmed-meshheading:18316587-Animals,
pubmed-meshheading:18316587-Bone and Bones,
pubmed-meshheading:18316587-Carcinoma, Renal Cell,
pubmed-meshheading:18316587-Cell Differentiation,
pubmed-meshheading:18316587-Cell Movement,
pubmed-meshheading:18316587-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:18316587-Humans,
pubmed-meshheading:18316587-Kidney Neoplasms,
pubmed-meshheading:18316587-Leukocytes, Mononuclear,
pubmed-meshheading:18316587-Macrophage Inflammatory Proteins,
pubmed-meshheading:18316587-Mice,
pubmed-meshheading:18316587-Neoplasm Metastasis,
pubmed-meshheading:18316587-Osteoclasts,
pubmed-meshheading:18316587-RANK Ligand,
pubmed-meshheading:18316587-Reverse Transcriptase Polymerase Chain Reaction
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| pubmed:year |
2008
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| pubmed:articleTitle |
Macrophage inflammatory protein-1 delta: a novel osteoclast stimulating factor secreted by renal cell carcinoma bone metastasis.
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| pubmed:affiliation |
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. kominsc@jhmi.edu
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| pubmed:publicationType |
Journal Article
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