Distinct signal transduction pathways are utilized during the tube formation and survival phases of in vitro angiogenesis

J Cell Sci. 1998 Dec 18:111 ( Pt 24):3621-31. doi: 10.1242/jcs.111.24.3621.

Abstract

Angiogenesis, the formation of new blood vessels from pre-existing ones, occurs during development, wound healing and cancer and involves stages that orchestrate a network of cooperative interactions. Peptide growth factors and extracellular matrix (ECM) components are two major groups of angiogenesis mediators. Among the different ECM proteins, collagens have been well-associated with in vivo angiogenesis. Using human umbilical vein endothelial cells (HUVEC) grown in 3-D collagen gels we show that: (1) HUVEC do not survive well in 3-D collagen gels due to rapid induction of apoptosis. (2) VEGF, a potent in vivo angiogenic factor, fails to induce tube formation. (3) PMA was effective in inducing tube formation and survival in HUVEC dispersed in 3-D collagen gels, activating MAP kinase, phosphoinositide 3-OH kinase (PI-3-kinase) and Akt/PKB (protein kinase B) pathways. (4) VEGF was effective in preventing PMA-induced tube-like structure regression after PMA-withdrawal by (5) activating the mitogen activated protein kinase (MAPK), rather than the Akt/PKB, signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / drug effects
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / pharmacology
  • Capillaries / drug effects
  • Capillaries / growth & development
  • Cell Culture Techniques
  • Cell Line
  • Cell Survival / drug effects
  • Collagen / pharmacology
  • Endothelial Growth Factors / pharmacology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / growth & development
  • Endothelium, Vascular / physiology*
  • Extracellular Matrix / physiology
  • Humans
  • Lymphokines / pharmacology
  • Neovascularization, Physiologic* / drug effects
  • Phosphatidylinositol 3-Kinases / pharmacology
  • Phosphorylation / drug effects
  • Protein Kinase C / pharmacology
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Proto-Oncogene Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Collagen
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Tetradecanoylphorbol Acetate