ABSTRACT
HGF/SF is a multifunctional cytokine which through binding to its cellular receptor, c-MET, can elicit mitogenic, morphogenic and motogenic responses in target cells. Expression of HGF/SF and c-MET has been shown to be critical in early embryogenesis affecting development of many organs and tissues. The effects of HGF/SF4 on established human and mouse mammary cell lines have previously been reported. This review describes the source and targets for HGF/SF in both human and mouse mammary tissue and discusses the effects of HGF/SF on primary mouse and human mammary epithelial cells in vitro, detailing the individual response of the two epithelial sub-population of cells which comprise this organ. Additionally, the effects of HGF/SF overexpression on mouse mammary gland development in vivo, are summarized.
Subject(s)
Breast/embryology , Epithelial Cells/physiology , Hepatocyte Growth Factor/physiology , Mammary Glands, Animal/embryology , Animals , Cells, Cultured , Female , Humans , Mice , MorphogenesisABSTRACT
We have recently demonstrated the regulated expression of HGF/SF and its receptor (c-met) during mouse mammary gland development together with the mitogenic, motogenic and morphogenic effects of exogenous HGF/SF on primary mammary epithelial cells in culture. This study was undertaken to analyze the influence of HGF/SF on reconstituted mouse mammary gland development in vivo. Here we report that overexpression of HGF/SF induces a range of alterations in the architecture of virgin mouse mammary gland. These include an enhancement of ductal end bud (mammary gland morphoregulatory control point) size and numbers and hyperplastic branching morphogenesis. These data are the first demonstration of the effects of HGF/SF on mammary epithelium in vivo.
Subject(s)
Breast/cytology , Breast/growth & development , Hepatocyte Growth Factor/physiology , Animals , Female , Gene Transfer Techniques , Genetic Vectors , Mice , RetroviridaeABSTRACT
The mammary gland is a renewing tissue in which morphogenetic processes and differentiation occur cyclically during the menstrual cycle, pregnancy and lactation. These events have been shown to be dependent upon epithelial-mesenchymal interactions. Studies of the effects of individual factors, their cellular source and their target cell populations in the different developmental stages of the mammary gland are greatly facilitated by the accessibility of this organ and the application of new techniques that allow purification of the major epithelial and stromal components of this tissue. Here we demonstrate that HGF/SF and its cellular receptor, c-met, are expressed and regulated temporally during mouse mammary development and differentiation. We show that human and mouse mammary fibroblasts produce HGF/SF and that HGF/SF is not only mitogenic but morphogenic and motogenic for both human and mouse mammary epithelial cells. We have found that human luminal and myoepithelial cells express c-met differentially and that HGF/SF has different effects on these two mammary epithelial cell populations. HGF/SF is mitogenic for luminal cells but not myoepithelial cells, and morphogenic to myoepithelial cells but not luminal cells. This is discussed in the context of the proliferative compartments in the normal mammary gland and the potential role of the myoepithelial cells to act as the skeleton for ductal development.
Subject(s)
Breast/growth & development , Hepatocyte Growth Factor/physiology , Mammary Glands, Animal/growth & development , Animals , Base Sequence , Blotting, Northern , Breast/cytology , Cell Division/physiology , Cell Line , Cell Movement , DNA Primers/genetics , Dogs , Epithelium/physiology , Female , Fibroblasts/physiology , Gene Expression , Hepatocyte Growth Factor/genetics , Humans , Mammary Glands, Animal/cytology , Molecular Sequence Data , Morphogenesis , Polymerase Chain Reaction , Proto-Oncogene Proteins c-met , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/physiologyABSTRACT
In 80% of a random sample the extensor ossis metatarsi hallucis was present. In 90% of these occurrences it arose off the medial aspect of the extensor hallucis longus tendon and coursed distally, medially, and inferiorly an average of 4.0 cm., inserting into the sling portion of the extensor apparatus. Variation of this insertion occurred in 10% of the cases in which the sling portion of the extensor apparatus continued to illustrate fibers of the extensor ossis metatarsi hallucis inserting into it. There is little variation in the occurrence of this tendon between the sexes. The frequency of occurrence of the extensor ossis metatarsi hallucis from this study supports a theory that this tendon should be considered to occur as a rule rather than an exception, and because the previously suggested name of extensor hallucis capsularis is not biomechanically sound, perhaps the tendon merely be termed the secondary extensor hallucis longus.
