Identification of angiogenic properties of insulin-like growth factor II in in vitro angiogenesis models.
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.
Lee
O H
OH
Department of Molecular Biology, Pusan National University, Korea.
Bae
S K
SK
Bae
M H
MH
Lee
Y M
YM
Moon
E J
EJ
Cha
H J
HJ
Kwon
Y G
YG
Kim
K W
KW
D002465:Cell Movement / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002633:Chemotaxis; D004847:Epithelial Cells; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D014470:Umbilical Cord / Q000098:blood supply / Q000166:cytology
D007335:Insulin-Like Growth Factor II