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Human Angiostatin Inhibits Murine Hemangioendothelioma Tumor Growth in Vivo¹

Departments of Pediatrics [B. J. L., M. E. Q., A. S. P.], Dermatology [A. S. P.], and Medicine, Division of Hematology/Oncology [S. T. G., G. A. S.], Northwestern University Medical School, Chicago, Illinois 60611

Angiostatin inhibits angiogenesis and metastatic tumor growth; however, its usefulness in treating primary nonmetastasizing tumors is less well understood. We now report the effectiveness of human angiostatin administration in a mouse hemangioendothelioma model. Human angiostatin was administered to mice with s.c. hemangioendothelioma and associated disseminated intravascular coagulopathy (Kasabach-Merritt syndrome). Angiostatin significantly reduced tumor volume in comparison to nontreated controls, increased survival, and prevented the profound thrombocytopenia and anemia of Kasabach-Merritt syndrome. Apoptosis of tumor cells was induced by angiostatin, but tumor cell proliferation was not inhibited. These data suggest angiostatin as a novel treatment for nonmetastasizing vascular tumors and for Kasabach-Merritt syndrome.

¹ This work was supported by March of Dimes Grant 96-0455 (to A. S. P.), grants from the Dermatology Foundation Dermik (to A. S. P.) and Feinberg Cardiovascular Research Institute, a grant-in-aid from the American Cancer Society, Illinois Division, and NIH Grant CA71875 (to G. A. S.).

² To whom requests for reprints should be addressed, at Division of Dermatology #107, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614. Phone: (773) 880-3681; Fax: (773) 880-3025; E-mail: apaller@nwu.edu.

Received 8/28/97. Accepted 10/17/97.

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