Divergent Matrix-Remodeling Strategies Distinguish Developmental from Neoplastic Mammary Epithelial Cell Invasion Programs.
Dev Cell
; 47(2): 145-160.e6, 2018 10 22.
Article
em En
| MEDLINE
| ID: mdl-30269950
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metaloproteinase 14 da Matriz
/
Invasividade Neoplásica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Dev Cell
Assunto da revista:
EMBRIOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article