Angiostatin upregulates E-selectin in proliferating endothelial cells.
Angiostatin, a 38 kilodalton fragment of plasminogen, is a potent inhibitor of angiogenesis. However, little is known about how angiostatin affects endothelial gene expression. To learn more about its effect on endothelial-specific genes implicated in angiogenesis, we examined E-selectin expression and function in bovine capillary endothelial cells treated with recombinant angiostatin. Angiostatin caused a four to five-fold increase in E-selection polypeptide levels in proliferating endothelial cells but little or no increase in confluent cells. P-selection polypeptide levels were unaffected by angiostatin in either proliferating or confluent cells. E-selectin mRNA and adhesion activity in proliferating endothelial cells were also increased by angiostatin. Angiostatin had little effect on the distribution of endothelial cells in G0/G1, S, and G2/M, indicating angiostatin does not alter cell cycle progression significantly. These data demonstrate that angiostatin selectively upregulates E-selectin in proliferating endothelial cells in vitro. This selectivity may provide insights into the mechanism by which angiostatin inhibits tumor growth in vivo without apparent effects on quiescent endothelium.
Luo
J
J
Surgical Research Laboratory, Children's Hospital, Boston, Massachusetts 02115, USA.
Lin
J
J
Paranya
G
G
Bischoff
J
J
D043168:Angiostatins; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured; D003510:Cyclohexanes; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010446:Peptide Fragments / Q000494:pharmacology*; D010958:Plasminogen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D003510:Cyclohexanes; D019040:E-Selectin; D010446:Peptide Fragments; D012333:RNA, Messenger; D012717:Sesquiterpenes; D043168:Angiostatins; D010958:Plasminogen; D000077609:O-(Chloroacetylcarbamoyl)fumagillol