Vitamin D binding protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and tumor growth in mice.
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.
Kisker
Oliver
O
Division of Surgical Research, Children's Hospital, Boston, MA 02115, USA.
Onizuka
Shinya
S
Becker
Christian M
CM
Fannon
Michael
M
Flynn
Evelyn
E
D'Amato
Robert
R
Zetter
Bruce
B
Folkman
Judah
J
Ray
Rahul
R
Swamy
Narasimha
N
Pirie-Shepherd
Steven
S
D000482:Allantois / Q000166:cytology / Q000187:drug effects; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo / Q000378:metabolism; D002823:Chorion / Q000166:cytology / Q000187:drug effects; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors / Q000494:pharmacology*; D008264:Macrophages; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009439:Neuraminidase / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000637:transplantation; D014809:Vitamin D-Binding Protein / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000378:metabolism
D017077:Culture Media, Conditioned; D016215:Macrophage-Activating Factors; D014809:Vitamin D-Binding Protein; C101908:vitamin D-binding protein-macrophage activating factor; D009439:Neuraminidase; D001616:beta-Galactosidase