Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascular endothelial cells

Jpn J Cancer Res. 1994 Jan;85(1):53-62. doi: 10.1111/j.1349-7006.1994.tb02886.x.

Abstract

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.

MeSH terms

  • Cell Line
  • ErbB Receptors / analysis
  • Hepatocyte Growth Factor / chemistry
  • Hepatocyte Growth Factor / physiology*
  • Humans
  • Neovascularization, Pathologic / etiology
  • Plasminogen Activators / metabolism
  • Plasminogen Activators / physiology*
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Transforming Growth Factor alpha / analysis

Substances

  • Transforming Growth Factor alpha
  • Hepatocyte Growth Factor
  • ErbB Receptors
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases
  • Plasminogen Activators