Identification of angiogenic properties of insulin-like growth factor II in in vitro angiogenesis models

Br J Cancer. 2000 Jan;82(2):385-91. doi: 10.1054/bjoc.1999.0931.


Insulin-like growth factor II (IGF-II), highly expressed in a number of human tumours, has been recently known to promote neovascularization in vivo. Yet, the detailed mechanism by which IGF-II induces angiogenesis has not been well defined. In the present study, we explored an angiogenic activity of IGF-II in in vitro angiogenesis model. Human umbilical vein endothelial cells (HUVECs) treated with IGF-II rapidly aligned and formed a capillary-like network on Matrigel. In chemotaxis assay, IGF-II remarkably increased migration of HUVECs. A rapid and transient activation of p38 mitogen-activated protein kinase (p38 MAPK) and p125 focal adhesion kinase (p125FAK) phosphorylation was detected in HUVECs exposed to IGF-II. IGF-II also stimulated invasion of HUVECs through a polycarbonate filter coated with Matrigel. Quantitative gelatin-based zymography identified that matrix metalloproteinase-2 (MMP-2) activity generated from HUVECs was increased by IGF-II. This induction of MMP-2 activity was correlated with Northern blot analysis, showing in HUVECs that IGF-II increased the expression of MMP-2 mRNA, while it did not affect that of TIMP-2, a tissue inhibitor of MMP-2. These results provide the evidence that IGF-II directly induces angiogenesis by stimulating migration and morphological differentiation of endothelial cells, and suggest that IGF-II may play a crucial role in the progression of tumorigenesis by promoting the deleterious neovascularization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement / physiology*
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • Chemotaxis*
  • Epithelial Cells
  • Humans
  • Insulin-Like Growth Factor II / pharmacology*
  • Neoplasm Invasiveness / physiopathology
  • Neovascularization, Pathologic / physiopathology*
  • Umbilical Cord / blood supply
  • Umbilical Cord / cytology


  • Insulin-Like Growth Factor II