The angiogenesis inhibitor AGM-1470 selectively increases E-selectin.
The levels of E-selectin mRNA and protein were analyzed in bovine capillary cells treated with or without the angiogenesis inhibitor AGM-1470 (also known as TNP-470). Cells treated with AGM-1470 had a two- to sevenfold (median fivefold) increase in E-selectin mRNA compared with little or no increase in P-selectin, PECAM-1 and VCAM-1 mRNA. E-selectin protein was also significantly increased after exposure to AGM-1470. In contrast, there was no detectable effect on PECAM-1 protein. The increase in E-selectin mRNA and protein was always greater with subconfluent growing cells than with confluent cells. This apparent resistance of confluent endothelial cells to AGM-1470 may be relevant to its specificity in vivo. The fact that the effect of AGM-1470 on E-selectin is relatively selective for subconfluent growing cells may provide a clue as to how AGM-1470 is able to both reversibly inhibit endothelial cell proliferation in vitro and inhibit tumor growth in vivo without apparent effects to quiescent endothelium.
Budson
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Surgical Research Laboratory, Children's Hospital, Boston, Massachusetts 02115, USA.
Ko
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Brasel
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Bischoff
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D000302:Adrenal Cortex / Q000098:blood supply; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D002196:Capillaries; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003510:Cyclohexanes; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D019007:P-Selectin / Q000096:biosynthesis; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012717:Sesquiterpenes / Q000494:pharmacology*; D014158:Transcription, Genetic; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000903:Antibiotics, Antineoplastic; D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D003510:Cyclohexanes; D019040:E-Selectin; D019007:P-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D012717:Sesquiterpenes; D019010:Vascular Cell Adhesion Molecule-1; D000077609:O-(Chloroacetylcarbamoyl)fumagillol