The tetrapeptide AcSDKP, an inhibitor of primitive hematopoietic cell proliferation, induces angiogenesis in vitro and in vivo

• Published in: Blood Vol. 101; no. 8; pp. 3014 - 3020
• Main Authors: Liu, Jian-Miao, Lawrence, Françoise, Kovacevic, Milica, Bignon, Jérôme, Papadimitriou, Evangelia, Lallemand, Jean-Yves, Katsoris, Panagiotis, Potier, Pierre, Fromes, Yves, Wdzieczak-Bakala, Joanna
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.04.2003; The Americain Society of Hematology
• Subjects: Abdominal Wall - blood supply; Adenocarcinoma - pathology; Allantois - blood supply; Animals; Biological and medical sciences; Cell Differentiation - drug effects; Cell Fusion; Cell Line, Transformed; Cell Movement - drug effects; Cells, Cultured - drug effects; Chick Embryo; Chorion - blood supply; Collagen; Combined treatment; Drug Combinations; Drug Implants; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Enzyme Activation - drug effects; Enzyme Induction - drug effects; Humans; Laminin; Lung Neoplasms - pathology; Matrix Metalloproteinase 1 - biosynthesis; Matrix Metalloproteinase 1 - metabolism; Medical sciences; Neovascularization, Physiologic - drug effects; Oligopeptides - administration & dosage; Oligopeptides - chemical synthesis; Oligopeptides - pharmacology; Proteoglycans; Rats; Rats, Wistar; Treatment. General aspects; Tumor Cells, Cultured; Tumors; Umbilical Veins - cytology; Endothelial cell; Rat; Enzyme; Rodentia; Metalloendopeptidases; In vitro; Peptidases; Angiogenesis; In vivo; Vertebrata; Mammalia; Tetrapeptide; Animal; Bone marrow; Hydrolases; Interstitial collagenase
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-07-2315

The tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP), purified from bone marrow and constitutively synthesized in vivo, belongs to the family of negative regulators of hematopoiesis. It protects the stem cell compartment from the toxicity of anticancer drugs and irradiation and consequently contributes to a reduction in marrow failure. This current work provides experimental evidence for another novel biologic function of AcSDKP. We report that AcSDKP is a mediator of angiogenesis, as measured by its ability to modulate endothelial cell function in vitro and angiogenesis in vivo. AcSDKP at nanomolar concentrations stimulates in vitro endothelial cell migration and differentiation into capillary-like structures on Matrigel as well as enhances the secretion of an active form of matrix metalloproteinase-1 (MMP-1). In vivo, AcSDKP promotes a significant angiogenic response in the chicken embryo chorioallantoic membrane (CAM) and in the abdominal muscle of the rat. Moreover, it induces the formation of blood vessels in Matrigel plugs implanted subcutaneously in the rat. This is the first report demonstrating the ability of AcSDKP to interact directly with endothelial cells and to elicit an angiogenic response in vitro and in vivo.