Squalamine inhibits angiogenesis and solid tumor growth in vivo and perturbs embryonic vasculature.
The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in multiple animal models. This effect is mediated, at least in part, by blocking mitogen-induced proliferation and migration of endothelial cells, thus preventing neovascularization of the tumor. Squalamine has no observable effect on unstimulated endothelial cells, is not directly cytotoxic to tumor cells, does not alter mitogen production by tumor cells, and has no obvious effects on the growth of newborn vertebrates. Squalamine was also found to have remarkable effects on the primitive vascular bed of the chick chorioallantoic membrane, which has striking similarities to tumor capillaries. Squalamine may thus be well suited for treatment of tumors and other diseases characterized by neovascularization in humans.
Sills
A K
AK
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Williams
J I
JI
Tyler
B M
BM
Epstein
D S
DS
Sipos
E P
EP
Davis
J D
JD
McLane
M P
MP
Pitchford
S
S
Cheshire
K
K
Gannon
F H
FH
Kinney
W A
WA
Chao
T L
TL
Donowitz
M
M
Laterra
J
J
Zasloff
M
M
Brem
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo / Q000187:drug effects; D002777:Cholestanols / Q000494:pharmacology; D003094:Collagen; D003315:Cornea; D016510:Corneal Neovascularization / Q000517:prevention & control; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D005134:Eye Neoplasms / Q000517:prevention & control; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy / Q000473:pathology; D007797:Laminin; D008222:Lymphokines / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011509:Proteoglycans; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016588:Anticarcinogenic Agents; D002777:Cholestanols; D004338:Drug Combinations; D016228:Endothelial Growth Factors; D007797:Laminin; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen; C079655:squalamine