[Effects of endocrine peptides on proliferation, migration and differentiation of human endothelial cells].
OBJECTIVE
We aimed to evaluate the effects of several peptides (substance P, VIP, neuropeptide Y, bombesin, glucagon and somatostatin) on the proliferation, migration and differentiation of human endothelial cells and their modulation by an anti-angiogenic factor, endostatin.


METHODS
Human endothelial cells (HUVEC) were isolated from umbilical veins. Their proliferation was measured by the incorporation of tritiated thymidine. Their migration was evaluated by using an haptotactic assay performed in Boyden chambers, after metabolic labeling of HUVEC through (35) S-methionin. Differentiation was evaluated as the capacity for HUVEC to form capillaries.


RESULTS
Endothelial cell proliferation was increased by neuropeptide Y, bombesin and glucagon. Somatostatin induced a significant decrease in basal and stimulated endothelial cell proliferation. The migration of HUVEC increased in the presence of substance P, VIP, neuropeptide Y, bombesin, glucagon and somatostatin. The number of capillaries was increased by substance P and VIP and decreased by neuropeptide Y, bombesin and somatostatin. Endostatin induced a significant decrease in endothelial cell proliferation in the basal state and after stimulation by neuropeptide Y and bombesin. Endostatin had no additive effect on the anti-proliferative action of somatostatin.


CONCLUSIONS
Our results suggest a role for endocrine peptides in the regulation of tumor angiogenesis. The potent anti-angiogenic effect of somatostatin may promote new therapeutic strategies.
Marion-Audibert
A M
AM
CNRS UMR 5578, Faculté de Médecine Rockefeller, Lyon.
Nejjari
M
M
Pourreyron
C
C
Anderson
W
W
Gouysse
G
G
Jacquier
M F
MF
Dumortier
J
J
Scoazec
J Y
JY
D001839:Bombesin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D043169:Endostatins; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D009478:Neuropeptide Y / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014471:Umbilical Veins; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D043169:Endostatins; D009478:Neuropeptide Y; D009479:Neuropeptides; D010446:Peptide Fragments; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D003094:Collagen; D005934:Glucagon; D001839:Bombesin