Abstract：
: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.
journal_name
Dev Celljournal_title
Developmental cellauthors
Feinberg TY,Zheng H,Liu R,Wicha MS,Yu SM,Weiss SJdoi
10.1016/j.devcel.2018.08.025subject
Has Abstractpub_date
2018-10-22 00:00:00pages
145-160.e6issue
2eissn
1534-5807issn
1878-1551pii
S1534-5807(18)30698-1journal_volume
47pub_type
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