Stimulation of DNA synthesis and cell proliferation of human mammary myoepithelial-like cells by hepatocyte growth factor/scatter factor depends on heparan sulfate proteoglycans and sustained phosphorylation of mitogen-activated protein kinases p42/44.
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.
Sergeant
N
N
School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, University of Manchester, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom.
Lyon
M
M
Rudland
P S
PS
Fernig
D G
DG
Delehedde
M
M
D001940:Breast / Q000166:cytology*; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation
D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D017228:Hepatocyte Growth Factor; D003094:Collagen; D020928:Mitogen-Activated Protein Kinases