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Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells

Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cel...

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Detalles Bibliográficos
Autores principales: Hirai, Yohei, Lochter, André, Galosy, Sybille, Koshida, Shogo, Niwa, Shinichiro, Bissell, Mina J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1998
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132590/
https://www.ncbi.nlm.nih.gov/pubmed/9425164
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author Hirai, Yohei
Lochter, André
Galosy, Sybille
Koshida, Shogo
Niwa, Shinichiro
Bissell, Mina J.
author_facet Hirai, Yohei
Lochter, André
Galosy, Sybille
Koshida, Shogo
Niwa, Shinichiro
Bissell, Mina J.
author_sort Hirai, Yohei
collection PubMed
description Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.
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spelling pubmed-21325902008-05-01 Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells Hirai, Yohei Lochter, André Galosy, Sybille Koshida, Shogo Niwa, Shinichiro Bissell, Mina J. J Cell Biol Article Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized. The Rockefeller University Press 1998-01-12 /pmc/articles/PMC2132590/ /pubmed/9425164 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Hirai, Yohei
Lochter, André
Galosy, Sybille
Koshida, Shogo
Niwa, Shinichiro
Bissell, Mina J.
Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells
title Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells
title_full Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells
title_fullStr Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells
title_full_unstemmed Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells
title_short Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells
title_sort epimorphin functions as a key morphoregulator for mammary epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132590/
https://www.ncbi.nlm.nih.gov/pubmed/9425164
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