Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascular endothelial cells.
Epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) stimulated cell migration, chemotaxis, and the expression of tissue-type plasminogen activator (t-PA) in human omental microvascular endothelial (HOME) cells. Hepatocyte growth factor (HGF) stimulated cell proliferation, but had a negligible stimulatory effect on cell migration, the expression of t-PA and tube-like formation into collagen gel in HOME cells. Basic fibroblast growth factor stimulated cell proliferation, cell migration, tubulogenesis and the expression of urokinase-type plasminogen activator (u-PA) in bovine aortic endothelial (BAE) cells. HOME and BAE cells had both high- and low-affinity receptors for HGF. In BAE cells, u-PA activity and tube-like structures in collagen gel were induced in the presence of HGF alone. In contrast, in HOME cells, t-PA activity and tube-like structures were induced in the presence of TGF-alpha alone, but not in the presence of HGF alone. However, we observed a marked induction of tube formation by HOME cells when both t-PA and HGF were added simultaneously. In the model system for tumor angiogenesis, when HOME cells were co-cultured with a renal cancer cell line, KPK13, tube-like structures were induced in the presence of HGF:KPK13 cells expressed large amounts of t-PA mRNA. Our present study suggested that HGF in concert with active t-PA could be angiogenic in HOME cells.
Morimoto
A
A
Department of Biochemistry, Oita Medical University.
Tada
K
K
Nakayama
Y
Y
Kohno
K
K
Naito
S
S
Ono
M
M
Kuwano
M
M
D002460:Cell Line; D066246:ErbB Receptors / Q000032:analysis; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000209:etiology; D010960:Plasminogen Activators / Q000378:metabolism / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000032:analysis
D016211:Transforming Growth Factor alpha; D017228:Hepatocyte Growth Factor; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D010960:Plasminogen Activators