Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prostate cancer cells.
BACKGROUND
Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors.


RESULTS
In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry studies with annexin V and propidium iodide showed that this inhibitory activity is not due to apoptosis or cell death. DBP-maf also had the ability to inhibit migration of prostate cancer cells in vitro. Finally, DBP-maf was shown to cause a reduction in urokinase plasminogen activator receptor (uPAR) expression in prostate tumor cells. There is evidence that activation of this receptor correlates with tumor metastasis.


CONCLUSIONS
These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of its macrophage activation.
Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, United States of America.
Kalvin J
KJ
Gregory
Bing
B
Zhao
Diane R
DR
Bielenberg
Sami
S
Dridi
Jason
J
Wu
Weihua
W
Jiang
Bin
B
Huang
Steven
S
Pirie-Shepherd
Michael
M
Fannon
D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D017931:DNA Primers; D006801:Humans; D016215:Macrophage-Activating Factors / Q000502:physiology*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D014809:Vitamin D-Binding Protein / Q000502:physiology*
D017931:DNA Primers; D016215:Macrophage-Activating Factors; D014809:Vitamin D-Binding Protein; D014568:Urokinase-Type Plasminogen Activator