10-18-2010 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. Methods and Findings: 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. Citation: Gregory KJ, Zhao B, Bielenberg DR, Dridi S, Wu J, et al. (2010) Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, and uPAR Expression of Prostate Cancer Cells. PLoS ONE 5(10): e13428. doi:10.1371/journal.pone.0013428 Editor: Joseph Najbauer, City of Hope National Medical Center, United States of America Received January 21, 2010; Accepted September 10, 2010; Published October 18, 2010 Copyright: 2010 Gregory et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by Department of Defense (DOD) grant PC030286 and Research to Prevent Blindness Challenge Grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: michael.fannon@uky.edu . These authors contributed equally to this work.