Vitamin D Binding Protein-Macrophage Activating Factor (DBP-maf) Inhibits Angiogenesis and Tumor Growth in Mice

• Published in: Neoplasia (New York, N.Y.) Vol. 5; no. 1; pp. 32 - 40
• Main Authors: Kisker, Oliver, Onizuka, Shinya, Becker, Christian M., Fannon, Michael, Flynn, Evelyn, D'Amato, Robert, Zetter, Bruce, Folkman, Judah, Ray, Rahul, Swamy, Narasimha, Pirie-Shepherd, Steven
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2003; Elsevier
• Subjects: Allantois - cytology; Allantois - drug effects; angiogenesis; Animals; beta-Galactosidase - metabolism; carcinoma; Cattle; Cell Division - drug effects; Chick Embryo - metabolism; Chorion - cytology; Chorion - drug effects; Culture Media, Conditioned; Endothelium, Vascular - metabolism; Humans; Immunity, Cellular; Macrophage Activation; Macrophage-Activating Factors - pharmacology; Macrophages; Male; Mice; Mice, SCID; Neovascularization, Pathologic - prevention & control; Neuraminidase - metabolism; pancreas; Pancreatic Neoplasms - blood supply; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Survival Rate; Tumor Cells, Cultured - transplantation; vitamin D binding protein; Vitamin D-Binding Protein - pharmacology; macrophages; carcinoma; angiogenesis; pancreas; vitamin D binding protein
• ISSN: 1476-5586; 1522-8002; 1476-5586; 1522-8002
• DOI: 10.1016/S1476-5586(03)80015-5

We have isolated a selectively deglycosylated form of vitamin D binding protein (DBP-maf) generated from systemically available DBP by a human pancreatic cancer cell line. DBP-maf is anti proliferative for endothelial cells and antiangiogenic in the chorioallantoic membrane assay. DBP-maf administered daily was able to potently inhibit the growth of human pancreatic cancer in immune compromised mice (T/C=0.09). At higher doses, DBP-maf caused tumor regression. Histological examination revealed that treated tumors had a higher number of infiltrating macrophages as well as reduced microvessel density, and increased levels of apoptosis relative to untreated tumors. Taken together, these data suggest that DBP-maf is an antiangiogenic molecule that can act directly on endothelium as well as stimulate macrophages to attack both the endothelial and tumor cell compartment of a growing malignancy.