Inhibition of basic fibroblast growth factor and vasculotropin biological activities on cultured cells by almitrine.
Autonomous cell growth may result from interactions of cellular growth factors with their receptors leading to the establishment of external or internal autocrine loops which can induce tumor formation. Tumor progression above a small volume also requires an increase in blood supply. This is achieved by the release from the tumor of angiogenic growth factors which diffuse toward preexisting capillaries. The search for compounds interfering with growth factors and their receptors represents a field of investigation of increasing importance. In this report we show that almitrine interferes with the binding of basic fibroblast growth factor and vasculotropin/vascular endothelial growth factor to their receptors present on vascular endothelial cells, smooth muscle cells or retinal pigment epithelium. This molecule inhibits reversibly serum and basic growth factors stimulated cell growth and motility without affecting epidermal growth factor-stimulated proliferation.
Moukadiri
H
H
Laboratoire de Biologie Moléculaire des Eucaryotes, Toulouse, France.
Gouzi
L
L
Detolle-Sarbach
S
S
Guez
D
D
Plouët
J
J
D015765:Almitrine / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D006133:Growth Substances; D018121:Receptors, Cytokine; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C075217:vasculotropin receptor; D016222:Fibroblast Growth Factor 2; D015765:Almitrine