Source:http://linkedlifedata.com/resource/pubmed/id/18071307
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
23
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| pubmed:dateCreated |
2008-5-22
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| pubmed:abstractText |
Membrane-type I matrix metalloproteinase (MT1-MMP) is associated with multiple forms of cancer including mammary cancer. To directly evaluate the significance of MT1-MMP expression in tumor progression and metastasis using a genetically induced cancer model, we crossed MT1-MMP-deficient mice to MMTV-polyoma virus middle T-antigen (PyMT) mice. Expression of PyMT in the MT1-MMP-deficient background consistently resulted in hyperplasia of the mammary gland as seen in wild-type PyMT littermates. Following orthotopic transplantation of PyMT+ glands into the cleared mammary fat pad of syngeneic recipient mice, MT1-MMP-deficient tumors were palpable earlier than wild-type tumors. Moreover, MT1-MMP-deficient tumors grew to the experimental end point size quicker than control tumors, but demonstrated markedly reduced ability to metastasize to the lungs of recipient mice. Accordingly, MT1-MMP-deficient mice displayed an overall reduction in metastasis count of 50%. MT1-MMP was expressed solely in the stroma of PyMT-induced tumors and those metastatic nodules that formed in the lungs were devoid of MT1-MMP expression. Stromal fibroblasts isolated from MT1-MMP-deficient tumors did not degrade type I collagen suggesting that efficient dissemination of tumor cells is dependent on stromal cell remodeling of the tumor environment. The data demonstrate directly that MT1-MMP-mediated proteolysis by stromal cells is important in the metastatic process.
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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 |
May
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| pubmed:issn |
1476-5594
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
22
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| pubmed:volume |
27
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3274-81
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| pubmed:meshHeading |
pubmed-meshheading:18071307-Animals,
pubmed-meshheading:18071307-Carcinoma, Ductal, Breast,
pubmed-meshheading:18071307-Cell Proliferation,
pubmed-meshheading:18071307-Collagen,
pubmed-meshheading:18071307-Disease Progression,
pubmed-meshheading:18071307-Female,
pubmed-meshheading:18071307-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:18071307-Mammary Neoplasms, Experimental,
pubmed-meshheading:18071307-Matrix Metalloproteinase 14,
pubmed-meshheading:18071307-Mice,
pubmed-meshheading:18071307-Models, Biological,
pubmed-meshheading:18071307-Neoplasm Invasiveness,
pubmed-meshheading:18071307-Neoplasm Metastasis,
pubmed-meshheading:18071307-Protein Processing, Post-Translational,
pubmed-meshheading:18071307-Stromal Cells,
pubmed-meshheading:18071307-Tumor Cells, Cultured,
pubmed-meshheading:18071307-Up-Regulation
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| pubmed:year |
2008
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| pubmed:articleTitle |
MT1-MMP is required for efficient tumor dissemination in experimental metastatic disease.
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| pubmed:affiliation |
Matrix Metalloproteinase Unit, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892-4380, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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