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Cited by 391

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.

The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

Open access
Simian, Marina, Hirai, Yohei, Navre, Marc, Werb, Zena, Lochter, Andre, Bissell, Mina J.·2001·Development
DOI 10.1242/dev.128.16.3117
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Abstract

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a crucial role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

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Metadata

Authors
Simian, M., Hirai, Y., Navre, M., Werb, Z., Lochter, A., & Bissell, M. J.
Venue
Development
Publisher
The Company of Biologists
Published
2001-08-15
Volume
128
Issue
16
Pages
3117-3131
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.128.16.3117
OpenAlex
W2102003692
Cited by
391
References
49
FWCI
5.66
Type
journal article
Language
en
Open access
green

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