Metastasizing breast carcinoma cells have been hypothesized to mobilize tissue-invasive activity by co-opting the proteolytic systems employed by normal mammary epithelial cells undergoing branching morphogenesis. However, the critical effectors underlying morphogenesis remain unidentified, and their relationship to breast cancer invasion programs is yet to be established. Here, we identify the membrane-anchored matrix metalloproteinase, Mmp14/MT1-MMP, but not the closely related proteinase Mmp15/MT2-MMP, as the dominant proteolytic effector of both branching morphogenesis and carcinoma cell invasion in vivo. Unexpectedly, however, epithelial cell-specific targeting of Mmp14/MT1-MMP in the normal mammary gland fails to impair branching, whereas deleting the proteinase in carcinoma cells abrogates invasion, preserves matrix architecture, and completely blocks metastasis. By contrast, in the normal mammary gland, extracellular matrix remodeling and morphogenesis are ablated only when Mmp14/MT1-MMP expression is specifically deleted from the periductal stroma. Together, these findings uncover the overlapping but divergent strategies that underlie developmental versus neoplastic matrix remodeling programs.
Pubmed ID: 30269950 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsThis monoclonal targets F4/80 antibody [CI:A3-1]
View all literature mentionsThis polyclonal targets Ki67 antibody - Proliferation Marker
View all literature mentionsThis monoclonal targets Vimentin antibody [EPR3776]
View all literature mentionsThis unknown targets ZO-1
View all literature mentionsThis monoclonal targets MMP14
View all literature mentionsThis polyclonal targets Laminin antibody produced in rabbit
View all literature mentionsThis polyclonal targets Collagen Type IV
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsThis isotype control targets Not Applicable
View all literature mentionsThis monoclonal targets CD140a (PDGFRA)
View all literature mentionsThis polyclonal targets ND
View all literature mentionsThis polyclonal targets Mouse Keratin 5 (AF 138)
View all literature mentionsThis recombinant monoclonal targets YAP
View all literature mentionsThis polyclonal targets Phospho-Histone H3 (Ser10)
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets E-Cadherin (24E10) Rabbit mAb
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets Akt2
View all literature mentionsThis monoclonal targets Rat Mouse F4/80 Antigen-Pan Macrophage antibody Fitc Clone c1:a3-1
View all literature mentionsThis monoclonal targets CD16 / CD32
View all literature mentionsThis monoclonal targets E-cadherin
View all literature mentionsThis monoclonal targets 129/Sv mouse-derived endothelioma cell line tEnd.1
View all literature mentionsThis monoclonal targets Polyoma virus, Medium T antigen
View all literature mentionsThis polyclonal targets LYVE1 - Lymphatic Vessel Marker
View all literature mentionsThis monoclonal targets Cytokeratin 18
View all literature mentionsThis polyclonal targets alpha smooth muscle Actin
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsMus musculus with name FVB/N-Tg(MMTV-PyVT)634Mul/J from IMSR.
View all literature mentionsMus musculus with name STOCK Tg(MMTV-cre)1Mam/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6-Tg(CAG-EGFP)1Osb/J from IMSR.
View all literature mentionsMus musculus with name FVB/NJ from IMSR.
View all literature mentionsMus musculus with name B6.129X1-Twist2tm1.1(cre)Dor/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentions