PURPOSE: This study aims to investigate the role of gastrin-17 (G17) on 
angiogenesis features in gliomas both in vitro and in vivo.
EXPERIMENTAL DESIGN: The influences of G17 and G17 receptor antagonists were 
characterized in vitro in terms of angiogenesis on human umbilical vein 
endothelial cell (HUVEC) tubulogenesis processes on Matrigel and in vivo with 
respect to U373 orthotopic glioma xenografts. The influence of 
phosphatidylinositol 3'-kinase, protein kinase C, and nuclear factor-kappaB 
inhibitors was characterized in vitro on G17-mediated HUVEC tubulogenesis. 
G17-mediated release of interleukin (IL)-8 from HUVECs and G17-induced 
modifications in nuclear factor-kappaB DNA binding activity were characterized 
by means of specific enzyme-linked immunosorbent assays. The influence of G17 on 
E- and P-selectin expression was determined by means of computer-assisted 
microscopy, whereas the influence of E- and P-selectin on HUVEC migration was 
approached by means of antisense oligonucleotides. The chemotactic influence of 
G17 and IL-8 on HUVEC migration was characterized by means of computer-assisted 
videomicroscopy with Dunn chambers.
RESULTS: Messenger RNAs for cholecystokinin (CCK)A, CCKB, and CCKC receptors 
were present in HUVECs and microvessels dissected from a human glioblastoma. 
Whereas G17 significantly increased the levels of angiogenesis in vivo in the 
U373 experimental glioma model and in vitro in the HUVECs, the CCKB receptor 
antagonist L365,260 significantly counteracted the G17-mediated proangiogenic 
effects. G17 chemoattracted HUVECs, whereas IL-8 failed to do so. IL-8 receptor 
alpha (CXCR1) and IL-8 receptor beta (CXCR2) mRNAs were not detected in these 
endothelial cells. Gastrin significantly (but only transiently) decreased the 
level of expression of E-selectin, but not P-selectin, whereas IL-8 increased 
the expression of E-selectin. Specific antisense oligonucleotides against E- and 
P-selectin significantly decreased HUVEC tubulogenesis processes in vitro on 
Matrigel.
CONCLUSIONS: The present study shows that gastrin has marked proangiogenic 
effects in vivo on experimental gliomas and in vitro on HUVECs. This effect 
depends in part on the level of E-selectin activation, but not on IL-8 
expression/release by HUVECs.