Divergent Matrix-Remodeling Strategies Distinguish Developmental from Neoplastic Mammary Epithelial Cell Invasion Programs.

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 Cell

journal_title

Developmental cell

authors

Feinberg TY,Zheng H,Liu R,Wicha MS,Yu SM,Weiss SJ

doi

10.1016/j.devcel.2018.08.025

subject

Has Abstract

pub_date

2018-10-22 00:00:00

pages

145-160.e6

issue

2

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(18)30698-1

journal_volume

47

pub_type

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