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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.
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.
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.