Vitamin D binding protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and tumor growth in mice

Oliver Kisker1, Shinya Onizuka, Christian M Becker

  • 1Division of Surgical Research, Children's Hospital, Boston, MA 02115, USA.

Neoplasia (New York, N.Y.)
|March 28, 2003
PubMed

Insights

A modified vitamin D binding protein (DBP-maf) shows potent anti-cancer effects. This deglycosylated protein inhibits tumor growth, reduces blood vessel formation, and promotes cancer cell death in preclinical models.

Area of Science:

  • Biochemistry
  • Oncology
  • Immunology

Background:

  • Vitamin D binding protein (DBP) is a key player in vitamin D transport.
  • Pancreatic cancer remains a significant health challenge with limited treatment options.

Purpose of the Study:

  • To investigate the anti-cancer properties of a selectively deglycosylated form of DBP (DBP-maf).
  • To evaluate DBP-maf's efficacy as an antiangiogenic and antiproliferative agent against pancreatic cancer.

Main Methods:

  • Isolation of DBP-maf from a human pancreatic cancer cell line.
  • In vitro assessment of antiproliferative effects on endothelial cells.
  • In vivo efficacy studies in immunocompromised mice bearing human pancreatic tumors.
  • Histological analysis of tumor tissues, including microvessel density, macrophage infiltration, and apoptosis.

Main Results:

  • DBP-maf demonstrated potent antiangiogenic activity in the chorioallantoic membrane assay.
  • Daily administration of DBP-maf significantly inhibited pancreatic tumor growth (T/C=0.09) and induced tumor regression at higher doses.
  • Histological analysis revealed reduced microvessel density, increased macrophage infiltration, and elevated apoptosis in DBP-maf treated tumors.

Conclusions:

  • DBP-maf exhibits significant antiangiogenic and direct anti-tumor effects.
  • DBP-maf acts by inhibiting endothelial cell proliferation and stimulating macrophage-mediated tumor cell attack.
  • DBP-maf represents a promising therapeutic candidate for pancreatic cancer treatment.

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