Abstract
Hepatocyte growth factor/scatter factor (HGF/SF) is a heparan/dermatan sulfate-binding growth factor produced by stromal cells that acts as a paracrine effector on neighboring epithelia. HGF/SF stimulated DNA synthesis in human mammary (Huma) 109 myoepithelial-like cells grown on collagen I and fibronectin substrata but not when grown on plastic. Dual phosphorylation of mitogen-activated protein kinases (p42/44(MAPK)) was required for this stimulation of DNA synthesis. In Huma 109 cells cultured on plastic, HGF/SF stimulated a transient phosphorylation of p42/44(MAPK), which reached a maximum at 10 min after addition of the growth factor and returned to near basal levels after 20 min. In contrast, the phosphorylation of p42/44(MAPK) stimulated by HGF/SF in cells cultured on collagen I or fibronectin was sustained over 45 min. In Huma 109 cells deficient in sulfated glycosaminoglycans, HGF/SF failed to stimulate p42/44(MAPK) phosphorylation or DNA synthesis on any substratum, even when soluble heparan sulfate proteoglycans purified from the cells or from the culture medium were added. However, HGF/SF stimulated DNA synthesis and a sustained phosphorylation of p42/44(MAPK) in sulfated glycosaminoglycan-deficient Huma 109 cells plated on a substratum of medium HSPGs but not cell HSPGs. The HGF/SF-induced proliferation is thus highly dependent on heparan sulfate proteoglycans in myoepithelial-like cells.
Highlights
Hepatocyte growth factor/scatter factor (HGF/SF)1 is synthesized by cells in the stroma and stimulates the growth, motility, and morphogenesis of epithelial cells
HGF/SF Induces a Sustained Dual Phosphorylation of p42/ 44MAPK When human mammary (Huma) 109 Cells Are Plated on Fibronectin and Collagen I—We investigated the kinetics of p42/44MAPK dual phosphorylation following the addition of HGF/SF to Huma 109 cells plated on plastic, fibronectin, or collagen I substrata (Fig. 4)
These results showed that the stimulation of DNA synthesis and sustained phosphorylation of p42/44MAPK in Huma 109 myoepitheliallike cells were dependent on the anchorage of medium-derived heparan sulfate proteoglycans
Summary
Hepatocyte growth factor/scatter factor (HGF/SF)1 is synthesized by cells in the stroma and stimulates the growth, motility, and morphogenesis of epithelial cells. In Huma 109 cells deficient in sulfated glycosaminoglycans, HGF/SF failed to stimulate p42/44MAPK phosphorylation or DNA synthesis on any substratum, even when soluble heparan sulfate proteoglycans purified from the cells or from the culture medium were added. HGF/SF stimulated DNA synthesis and a sustained phosphorylation of p42/ 44MAPK in sulfated glycosaminoglycan-deficient Huma 109 cells plated on a substratum of medium HSPGs but not cell HSPGs. The HGF/SF-induced proliferation is highly dependent on heparan sulfate proteoglycans in myoepithelial-like cells.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.