Abstract
BackgroundVitamin 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.Methods and FindingsIn 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.ConclusionsThese studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of its macrophage activation.
Highlights
Vitamin D binding protein (DBP) is the main transporter of vitamin D in the bloodstream
We have demonstrated previously in a xenograft mouse model that D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of human pancreatic tumors and that its ability to inhibit tumor growth in vivo is due, in part, to its antiangiogenic properties [4]
This study investigated the role of DBP-maf in direct inhibition of activities such as proliferation, migration, and expression of urokinase plasminogen activator receptor (uPAR) that are related to tumor growth and metastasis
Summary
Vitamin D binding protein (DBP) is the main transporter of vitamin D in the bloodstream. In that study it was shown that DBP-maf is antiangiogenic based on the reduction of vessels in the chick chorioallantoic membrane, and based on reduced microvessel density in tumors. It has been suggested in other studies that its primary antitumor mechanisms are immunological, due to its activation of macrophages. Recent clinical studies by Yamamoto et al have shown potent anti-tumor activity, as well as activity against HIV [7,8,9,10] This activity was measured as a function of reduced serum levels of the enzyme a-N-acetylgalactosaminidase (nagalase). Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity 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
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