|
|
|
|
|
|
|
||
J. Cell Biol.,
Volume 140, Number 1, January 12, 1998 159-169
* Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720; and 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.
Biomedical Research and
Development Department, Sumitomo Electric Industries, Ltd., Yokohama 244, Japan
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
