Journal Article

Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, and uPAR Expression of Prostate Cancer Cells

Wu, Jason, Bielenberg, Diane R., Fannon, Michael, Jiang, Weihua, Dridi, Sami, Gregory, Kalvin J., Huang, Bin, Zhao, Bing, Pirie-Shepherd, Steven

2010

Overview

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. 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. These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of its macrophage activation.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Angiogenesis / Annexin V / Apoptosis / Base Sequence / Binding / Blood vessels / Bone cancer / Breast cancer / Cancer / Cancer cells / Cancer metastasis / Cancer treatment / Cell activation / Cell Biology / Cell death / Cell Line, Tumor / Cell Movement / Cell Proliferation / Cytometry / DNA Primers / Flow cytometry / Humans / Immune response / Immune system / Immunotherapy / Insulin-like growth factors / Iodides / Leukocyte migration / Lung cancer / Lupus / Macrophage colony stimulating factor / Macrophage-Activating Factors - physiology / Macrophages / Male / Metastases / Metastasis / Neovascularization / Oncology/Prostate Cancer / Pancreatic cancer / Pharmacology / Propidium iodide / Prostate cancer / Prostatic Neoplasms - metabolism / Prostatic Neoplasms - pathology / Protein binding / Proteins / Reverse Transcriptase Polymerase Chain Reaction / Tumor cell lines / Tumor cells / Tumors / U-Plasminogen activator / Urokinase / Urokinase-Type Plasminogen Activator - metabolism / Vitamin D / Vitamin D-Binding Protein - physiology