Matrix metalloproteinase 13 is induced in fibroblasts in polyomavirus middle T antigen-driven mammary carcinoma without influencing tumor progression

Nielsen, B. S., Egeblad, M., Rank, F., Askautrud, H. A., Pennington, C. J., Pedersen, T. X., Christensen, I. J., Edwards, D. R., Werb, Z., Lund, L. R. (2008) Matrix metalloproteinase 13 is induced in fibroblasts in polyomavirus middle T antigen-driven mammary carcinoma without influencing tumor progression. PLoS One, 3 (8). ISSN 19326203 (ISSN)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/18698413
DOI: 10.1371/journal.pone.0002959

Abstract

Matrix metalloproteinase (MMP) 13 (collagenase 3) is an extracellular matrix remodeling enzyme that is induced in myofibroblasts during the earliest invasive stages of human breast carcinoma, suggesting that it is involved in tumor progression. During progression of mammary carcinomas in the polyoma virus middle T oncogene mouse model (MMTV-PyMT), Mmp13 mRNA was strongly upregulated concurrently with the transition to invasive and metastatic carcinomas. As in human tumors, Mmp13 mRNA was found in myofibroblasts of invasive grade II and III carcinomas, but not in benign grade I and II mammary intraepithelial neoplasias. To determine if MMP13 plays a role in tumor progression, we crossed MMTV-PyMT mice with Mmp13 deficient mice. The absence of MMP13 did not influence tumor growth, vascularization, progression to more advanced tumor stages, or metastasis to the lungs, and the absence of MMP13 was not compensated for by expression of other MMPs or tissue inhibitor of metalloproteinases. However, an increased fraction of thin collagen fibrils was identified in MMTV- PyMT;Mmp13 -/- compared to MMTV-PyMT;Mmp13 +/+ tumors, showing that collagen metabolism was altered in the absence of MMP13. We conclude that the expression pattern of Mmp13 mRNA in myofibroblasts of invasive carcinomas in the MMTV-PyMT breast cancer model recapitulates the expression pattern observed in human breast cancer. Our results suggest that MMP13 is a marker of carcinoma-associated myofibroblasts of invasive carcinoma, even though it does not make a major contribution to tumor progression in the MMTV-PyMT breast cancer model. © 2008 Nielsen et al.

Item Type: Paper
Uncontrolled Keywords: collagenase 3 primer DNA virus T antigen collagen fibril matrix metalloproteinase messenger RNA tissue inhibitor of metalloproteinase tumor marker virus middle T antigen animal article biosynthesis cancer staging disease course enzymology experimental neoplasm female fibroblast genetics lung tumor metastasis mouse mouse mutant neovascularization (pathology) pathology vascularization virology advanced cancer animal cell animal experiment animal model animal tissue breast carcinogenesis breast carcinoma cancer growth cancer invasion collagen metabolism controlled study enzyme activity enzyme analysis gene expression profiling lung metastasis male myofibroblast nonhuman Polyoma virus protein expression tumor vascularization Animals Antigens, Polyomavirus Transforming Disease Progression DNA Primers Fibroblasts Lung Neoplasms Mammary Neoplasms, Animal Matrix Metalloproteinase 13 Mice Mice, Knockout Neoplasm Metastasis Neoplasm Staging Neovascularization, Pathologic Mouse mammary tumor virus Mus Polyomavirus
Subjects: diseases & disorders > cancer
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
diseases & disorders > cancer > cancer types > breast cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > metalloproteinases
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
diseases & disorders > cancer > cancer types
CSHL Authors:
Depositing User: Matt Covey
Date: 2008
Date Deposited: 14 Mar 2013 19:43
Last Modified: 14 Mar 2013 19:43
PMCID: PMC2493034
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27812

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