Synergism between gangliosides and basic fibroblastic growth factor in favouring survival, growth, and motility of capillary endothelium.
The experiments reported were motivated by the observation that in vivo gangliosides promoted angiogenesis when the dose of the angiogenic factor was too low to be effective (Ziche et al.: Laboratory Investigation 61:629-634, 1989). As an approach to understanding the mechanism of this modulatory effect, we analysed the influence that gangliosides have on survival, growth, and migration of capillary endothelium when an angiogenesis factor like basic fibroblast growth factor (bFGF) was present in the culture medium. Clones of bovine capillary endothelium were cultivated in media unable to sustain survival over a 72 h period. With this experimental approach, cell survival was evaluated after addition of either bFGF or gangliosides or both to the medium. The Boyden chamber procedure was utilized to measure the influence of bFGF or gangliosides on cell mobilization across a micropore filter. Low doses of both molecules, ineffective when added singly to the culture media, improved all three parameters when added in combination. A synergic effect between bFGF and the gangliosides (GM1, GD1b, GT1b) was observed for the improvement of survival or growth and for the acceleration of endothelial cell migration. The removal of sialic acid from the ganglioside molecule prevented any effect on all three parameters. The addition of sialic acid alone to cultures was also totally ineffective. In the adult organism most angiogenic events occur under conditions of tissue damage. The synergism between gangliosides and bFGF can be interpreted as the initial phase of a process for which endothelial cell survival is the indispensable first step in the formation of a new vascular network.
De Cristan
G
G
Department of Pathology, San Giovanni Battista Hospital, Turin, Italy.
Morbidelli
L
L
Alessandri
G
G
Ziche
M
M
Cappa
A P
AP
Gullino
P M
PM
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005732:Gangliosides / Q000494:pharmacology*
D005732:Gangliosides; D005346:Fibroblast Growth Factors