Abstract
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 antiproliferative 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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Allantois / cytology
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Allantois / drug effects
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Animals
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Cattle
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Cell Division / drug effects
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Chick Embryo / metabolism
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Chorion / cytology
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Chorion / drug effects
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Culture Media, Conditioned
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Endothelium, Vascular / metabolism
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Humans
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Immunity, Cellular
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Macrophage Activation
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Macrophage-Activating Factors / pharmacology*
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Macrophages
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Male
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Mice
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Mice, SCID
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Neovascularization, Pathologic / prevention & control*
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Neuraminidase / metabolism
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Pancreatic Neoplasms / blood supply*
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology*
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Survival Rate
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Tumor Cells, Cultured / transplantation
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Vitamin D-Binding Protein / pharmacology*
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beta-Galactosidase / metabolism
Substances
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Culture Media, Conditioned
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Macrophage-Activating Factors
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Vitamin D-Binding Protein
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vitamin D-binding protein-macrophage activating factor
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Neuraminidase
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beta-Galactosidase