Vitamin D binding
protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and
tumor growth in mice.
Division of Surgical Research, Children's
Hospital, Boston, MA 02115, USA.
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.