Br J Cancer 2000,
PMID: 10646893
Lee, O H; Bae, S K; Bae, M H; Lee, Y M; Moon, E J; Cha, H J; Kwon, Y G; Kim, K W
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.
Diseases/Pathways annotated by Medline MESH: Cell Transformation, Neoplastic, Neoplasm Invasiveness, Neovascularization, Pathologic
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Text Mining Data
matrix metalloproteinase-2 (MMP-2) → IGF-II: "
Quantitative gelatin based zymography identified that
matrix metalloproteinase-2 (MMP-2) activity generated from HUVECs was
increased by
IGF-II
"
MMP-2 ⊣ TIMP-2: "
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
"
Manually curated Databases
No curated data.