Nutrients 2013, 5(7), 2577-2589; doi:10.3390/nu5072577
Article

A Novel Role for a Major Component of the Vitamin D Axis: Vitamin D Binding Protein-Derived Macrophage Activating Factor Induces Human Breast Cancer Cell Apoptosis through Stimulation of Macrophages

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Received: 7 April 2013; in revised form: 24 June 2013 / Accepted: 24 June 2013 / Published: 8 July 2013
(This article belongs to the Special Issue Vitamin D and Human Health)
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Abstract: The role of vitamin D in maintaining health appears greater than originally thought, and the concept of the vitamin D axis underlines the complexity of the biological events controlled by biologically active vitamin D (1,25(OH)(2)D3), its two binding proteins that are the vitamin D receptor (VDR) and the vitamin D-binding protein-derived macrophage activating factor (GcMAF). In this study we demonstrate that GcMAF stimulates macrophages, which in turn attack human breast cancer cells, induce their apoptosis and eventually phagocytize them. These results are consistent with the observation that macrophages infiltrated implanted tumors in mice after GcMAF injections. In addition, we hypothesize that the last 23 hydrophobic amino acids of VDR, located at the inner part of the plasma membrane, interact with the first 23 hydrophobic amino acids of the GcMAF located at the external part of the plasma membrane. This al1ows 1,25(OH)(2)D3 and oleic acid to become sandwiched between the two vitamin D-binding proteins, thus postulating a novel molecular mode of interaction between GcMAF and VDR. Taken together, these results support and reinforce the hypothesis that GcMAF has multiple biological activities that could be responsible for its anti-cancer effects, possibly through molecular interaction with the VDR that in turn is responsible for a multitude of non-genomic as well as genomic effects.
Keywords: vitamin D; macrophages; breast cancer; human; apoptosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Thyer, L.; Ward, E.; Smith, R.; Fiore, M.G.; Magherini, S.; Branca, J.J.V.; Morucci, G.; Gulisano, M.; Ruggiero, M.; Pacini, S. A Novel Role for a Major Component of the Vitamin D Axis: Vitamin D Binding Protein-Derived Macrophage Activating Factor Induces Human Breast Cancer Cell Apoptosis through Stimulation of Macrophages. Nutrients 2013, 5, 2577-2589.

AMA Style

Thyer L, Ward E, Smith R, Fiore MG, Magherini S, Branca JJV, Morucci G, Gulisano M, Ruggiero M, Pacini S. A Novel Role for a Major Component of the Vitamin D Axis: Vitamin D Binding Protein-Derived Macrophage Activating Factor Induces Human Breast Cancer Cell Apoptosis through Stimulation of Macrophages. Nutrients. 2013; 5(7):2577-2589.

Chicago/Turabian Style

Thyer, Lynda; Ward, Emma; Smith, Rodney; Fiore, Maria G.; Magherini, Stefano; Branca, Jacopo J.V.; Morucci, Gabriele; Gulisano, Massimo; Ruggiero, Marco; Pacini, Stefania. 2013. "A Novel Role for a Major Component of the Vitamin D Axis: Vitamin D Binding Protein-Derived Macrophage Activating Factor Induces Human Breast Cancer Cell Apoptosis through Stimulation of Macrophages." Nutrients 5, no. 7: 2577-2589.


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