| Remodeling of the mammary microenvironment after lactation promotes breast tumor cell metastasis. | |
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MedLine Citation:
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PMID: 16436674 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mammary gland microenvironment during postlactational involution shares similarities with inflammation, including high matrix metalloproteinase activity, fibrillar collagen deposition, and release of bioactive fragments of fibronectin and laminin. Because inflammation can promote tumorigenesis, we evaluated whether the tissue microenvironment of the involuting gland is also promotional. Extracellular matrix was isolated from mammary glands of nulliparous rats or rats with mammary glands undergoing weaning-induced involution. Using these matrices as substratum, nulliparous matrix was found to promote ductal organization of normal mammary epithelial MCF-12A cells in three-dimensional culture and to suppress invasion of mammary tumor MDA-MB-231 cells in transwell filter assays. Conversely, involution matrix failed to support ductal development in normal cells and promoted invasiveness in tumor cells. To evaluate the effects of these matrices on metastasis in vivo, MDA-MB-231 cells, premixed with Matrigel, nulliparous matrix, or involution matrix, were injected into mammary fat pads of nude mice. Metastases to lung, liver, and kidney were increased in the involution matrix group, and correlated with a twofold increase in tumor vascular endothelial growth factor expression and increased angiogenesis. These data suggest that the mammary gland microenvironment becomes promotional for tumor cell dissemination during involution, thus providing a plausible mechanism to explain the high rate of metastases that occur with pregnancy-associated breast cancer. |
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Authors:
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Shauntae M McDaniel; Kristen K Rumer; Sandra L Biroc; Richard P Metz; Meenakshi Singh; Weston Porter; Pepper Schedin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The American journal of pathology Volume: 168 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-01-26 Completed Date: 2006-03-21 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 608-20 Citation Subset: AIM; IM |
Affiliation:
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AMC Cancer Research Center, Denver, Colorado, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Breast Neoplasms / pathology* Collagen / metabolism Drug Combinations Extracellular Matrix / pathology Female Humans Kidney Neoplasms / pathology, secondary* Lactation / physiology* Laminin / metabolism Liver Neoplasms / pathology, secondary* Lung Neoplasms / pathology, secondary* Mammary Glands, Animal / physiology* Mice Mice, Nude Neoplasm Invasiveness / pathology Neovascularization, Pathologic Pregnancy Pregnancy, Animal Proteoglycans / metabolism Rats Rats, Sprague-Dawley Vascular Endothelial Growth Factor A / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA85944/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Drug Combinations; 0/Laminin; 0/Proteoglycans; 0/Vascular Endothelial Growth Factor A; 119978-18-6/matrigel; 9007-34-5/Collagen |
| Comments/Corrections | |
Comment In:
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Am J Pathol. 2006 Feb;168(2):363-6
[PMID:
16436651
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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