Vitamin D-binding protein-derived MAF, and prostate cancer

Summary: MAF was lost or reduced in prostate cancer patients due to high levels of nagalase.Macrophages activated by MAF develop a considerable variation of receptors that recognize malignant cell surfaces.16 nonanemic prostate cancer patients received weekly administration of 100 nanograms of MAF , during which time their nagalase levels reduced.After 14 to 25 weeks all 16 patients had low nagalase levels equivalent to those of healthy people, indicating the patients were cancer free.No recurrence occurred for 7 years.

Cancer Immunol Immunother. 2012 Dec;61(12):2377-8. doi: 10.1007/s00262-012-1310-9. Epub 2012 Jun 28. PubMed PMID: 22740161.

Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prostate cancer cells

MAF shows a direct and potent effect on prostate tumour cells in the absence of macrophages.  It demonstrates a reduction in proliferation as well as metastic clones of these cells.Studies show that this is not due to the death of the cancer cells, but due to the reduction of multiplication.  MAF also prevents the migration of prostate cancer cells in the lab.It stopped the prostate cancer cells from producing a receptor, and evidence shows that this receptor correlates with metastasis.It concludes that MAF has strong inhibitory activity even in the absence of macrophages.

Gregory KJ, Zhao B, Bielenberg DR, Dridi S, Wu J, Jiang W, Huang B, Pirie-Shepherd S, Fannon M

Glycosylation status of vitamin D binding protein in cancer patients

Based on earlier studies, it appears that vitamin D binding protein (DBP) is significantly or completely deglycosylated in cancer patients, thus destroying the molecular precursor of the immunologically important MAF.  This investigation was to directly investigate the volume of the three sugar molecules of serum derived DBP in various cancers. This study showed that there was no significant depletion of the trisaccharide in the 56 patients relative to healthy controls.

This suggests that the hypotheses regarding the structural or molecular origins of GcMAF being a trisaccharide should be reconsidered.

PubMed PMID: 19642159

Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor

Serum Gc protein (known as vitamin D(3)-binding protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of prostate cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells.
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Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor

Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells.
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Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor

Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of breast cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Patient serum Nagalase activity is proportional to tumor burden. The deglycosylated Gc protein cannot be converted to MAF, resulting in no macrophage activation and immunosuppression.
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Pancreatic carcinogenesis: apoptosis and angiogenesis

Summary:

Cell death and the creation of blood supplies to the cells (angiogenesis) are processes that are changed with cancers.Several reports show that a tumor suppressor gene that is in pancreatic cancer and related to malignancy can induce cell death and reduce the blood supply.This study has discovered two new angiogenesis inhibitors- one of them being GcMAF, the other aaAT-III.These molecules were able to regress tumours in immunodeficient mice, and show potent inhibition of circulatory cell proliferation.The angiogenesis inhibitors induced tumour dormancy in the animal model
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Effect of salivary gland adenocarcinoma cell-derived alpha-N-acetylgalactosaminidase on the bioactivity of macrophage activating factor

Summary:

To study the effects of nagalase on the bioactivity of GcMAF.A cancer cell line with high levels of nagalase, produced by the human salivary gland (HSG), was studied.GcMAF prepared enzymatically was able to activate macrophages.However, GcMAF treated with nagalase did not do this.Thus, salivary gland cancer in this study was able to produce large quantities of nagalase, which inactivates GcMAF produced from GcProtein, resulting in reduced phagocytic activity.This study suggests that HSG nagalase acts as an immunodeficiency factor in cancer patients.
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