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Squalamine Inhibits Angiogenesis and Solid Tumor Growth in Vivo and Perturbs Embryonic Vasculature¹

Hunterian Neurosurgical Laboratory, Department of Neurosurgery [A. K. S., B. M. T., D. S. E., E. P. S., J. D. D., H. B.], Department of Neurology and the Kennedy Krieger Research Institute [J. L.], Division of Gastroenterology [M. D.], The John Hopkins University School of Medicine, Baltimore, Maryland 21205; Molecular Devices Corporation, Sunnyvale, California 94089 [S. P.]; Departments of Pathology and Orthopedic Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104 [F. H. G.]; and Magainin Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania 19462 [J. I. W., K. C., M. P. M., W. A. K., T. L. C., M. Z.]

The novel aminosterol, sualamine, 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.

¹ Supported by National Cancer Institute Grants NCDDG-CA 52857 (to H. B.), P20-CA60172 (to H. B. and J. L.), T32-CA09574 (to H. B., A. S., and J. D.), and NS-32148 (to J. L.) as well as a grant from Magainin Pharmaceuticals, Inc.

² To whom requests for reprints should be addressed, at Johns Hopkins School of Medicine, Hunterian 817, 725 North Wolfe Street, Baltimore, MD 21205. Phone: (410) 614-0477; Fax: (410) 614-0478; E-mail: hbrem@welchlink.welch.jhu.edu.

Received 3/ 6/98. Accepted 4/27/98.

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