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

Neoplasia. Jan-Feb 2003;5(1):32-40. doi: 10.1016/s1476-5586(03)80015-5.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allantois / cytology
  • Allantois / drug effects
  • Animals
  • 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
  • Pancreatic Neoplasms / blood supply*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Survival Rate
  • Tumor Cells, Cultured / transplantation
  • Vitamin D-Binding Protein / pharmacology*
  • beta-Galactosidase / metabolism

Substances

  • Culture Media, Conditioned
  • Macrophage-Activating Factors
  • Vitamin D-Binding Protein
  • vitamin D-binding protein-macrophage activating factor
  • Neuraminidase
  • beta-Galactosidase