Effects of Vitamin D3-Binding Protein-Derived Macrophage Activating Factor (GcMAF) on Angiogenesis (Abstract, Citationlinks)
Background: The vitamin D3-binding protein (Gc protein)-derived macrophage activating factor (GcMAF) activates tumoricidal macrophages against a variety of cancers indiscriminately. We investigated whether GcMAF also acts as an antiangiogenic factor on endothelial cells. Methods: The effects of GcMAF on angiogenic growth factor-induced cell proliferation, chemotaxis, and tube formation were examined in vitro by using cultured endothelial cells (murine IBE cells, porcine PAE cells, and human umbilical vein endothelial cells [HUVECs]) and in vivo by using a mouse cornea micropocket assay. Blocking monoclonal antibodies to CD36, a receptor for the antiangiogenic factor thrombospondin-1, which is also a possible receptor for GcMAF, were used to investigate the mechanism of GcMAF action.
Results: GcMAF inhibited the endothelial cell proliferation, chemotaxis, and tube formation that were all stimulated by fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor-A, or angiopoietin 2. FGF-2-induced neovascularization in murine cornea was also inhibited by GcMAF. Monoclonal antibodies against murine and human CD36 receptor blocked the antiangiogenic action of GcMAF on the angiogenic factor stimulation of endothelial cell chemotaxis.
Conclusions: In addition to its ability to activate tumoricidal macrophages, GcMAF has direct antiangiogenic effects on endothelial cells independent of tissue origin. Theantiangiogenic effects of GcMAF may be mediated through the CD36 receptor.
Effects of Vitamin D3-Binding Protein-Derived Macrophage Activating Factor (GcMAF) on Angiogenesis
Shigeru Kanda, Yasushi Mochizuki, Yasuyoshi Miyata, Hiroshi Kanetake, Nobuto Yamamoto
Affiliations of authors: S. Kanda, Department of Molecular Microbiology and Immunology, Division of Endothelial Cell Biology, and Department of Urology, Nagasaki University Graduate School of Medicine, Nagasaki, Japan; Y. Mochizuki, Y. Miyata, H. Kanetake, Department of Urology, Nagasaki University Graduate School of Medicine; N. Yamamoto, Socrates Institute for Therapeutic Immunology, Philadelphia, PA.
Correspondence to: Shigeru Kanda, M.D., Ph.D., Department of Molecular Microbiology and Immunology, Division of Endothelial Cell Biology, Nagasaki University Graduate School of Medicine, 1-7-1, Sakamoto, Nagasaki 852-8501, Japan (e-mail: email@example.com ).
Journal of the National Cancer Institute, Vol. 94, No. 17, 1311-1319, September 4, 2002
© 2002 Oxford University Press
JNCI Journal of the National Cancer Institute 2002 94(17):1311-1319; doi:10.1093/jnci/94.17.1311
© 2002 by Oxford University Press