Angiostatin induces mitotic cell death of proliferating endothelial cells.
Angiostatin is an inhibitor of tumor angiogenesis that induces regression of experimental tumors and enhances the antitumor effects of radiation therapy. We report that the cytotoxic effects of angiostatin are restricted to the proliferating endothelial cell population. In addition, angiostatin and ionizing radiation (IR) interact by inducing death of dividing endothelial cells. We also show that angiostatin and IR interact to inhibit endothelial cell migration. These findings demonstrate that angiostatin targets the proliferating tumor vasculature and provide a mechanistic basis for the cytotoxic interaction of angiostatin and IR.
Hari
D
D
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois 60637, USA.
Beckett
M A
MA
Sukhatme
V P
VP
Dhanabal
M
M
Nodzenski
E
E
Lu
H
H
Mauceri
H J
HJ
Kufe
D W
DW
Weichselbaum
R R
RR
D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology; D043168:Angiostatins; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology; D002417:Cattle; D016923:Cell Death / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002464:Cell Migration Inhibition; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D008938:Mitosis; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011839:Radiation, Ionizing; D011994:Recombinant Proteins / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010446:Peptide Fragments; D011994:Recombinant Proteins; D043168:Angiostatins; D010958:Plasminogen