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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-07-2315.
Submitted July 31, 2002
Accepted November 29, 2002
The tetrapeptide AcSDKP, an inhibitor of primitive hematopoietic cell proliferation, induces angiogenesis in vitro and in vivo
Jian-Miao Liu, Francoise Lawrence, Milica Kovacevic, Jerome S Bignon, Evangelia Papadimitriou, Jean-Yves Lallemand, Panagiotis Katsoris, Pierre Potier, Yves Fromes, and Joanna Wdzieczak-Bakala*
Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette, France
Department of Pharmacy, University of Patras, Patras, Greece
Department of Biology, University of Patras, Patras, Greece
U523, INSERM, Paris, France
* Corresponding author; email: Johanna.Bakala{at}icsn.cnrs-gif.fr.
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 biological 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 was shown to stimulate in vitro endothelial cell migration and differentiation into capillary-like structures on Matrigel as well as to enhance 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.
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