The test measures the activity of alfa-N-acetylgalactosaminidase (nagalase) in blood. Nagalase is an extracellular matrix-degrading enzyme that is (increased) secreted by cancerous cells in the process of tumour invasion. It also is an intrisic component of envelope protein of various virions, such as HIV and the influenza virus. It is secreted from virus-infected cells..1,3,4
Nagalase deglycosylates the vitamin D3-binding protein DBP (in humans better known as Gc-protein). Gc-protein is the precursor for the major macrophage-activating factor (MAF). Gc-protein carries one trisaccharide consisting of N-acetylgalactosamine with dibranched galactose and sialic acid termini. By the deglycosylation the (complete) trisaccharide is removed from the Gc-protein. The glycosylated Gc-protein cannot be converted to MAF anymore.
Normally MAF is produced from Gc-protein by sequential removal of the galactose and sialic acid termini from this protein by respectively beta-galactosidase of inflammation- primed B lymphocytes and sialidase of T lymphocytes, with N-acetylgalactosamine as the remaining sugar. Macrophage-activation for phagocytosis and antigen presentation is the first step in the immune development cascade. Lost precursor activity leads to immunosuppression.
Increased activity of nagalase has been detected in the blood of patients with a wide variety of cancers, like cancer of the prostate, breast, colon, lung, oesophagus, stomach, liver, pancreas, kidney, bladder, testis, uterus and ovary, mesothelioma, melanoma, fibrosarcoma, glioblastoma, neuroblastoma and various leukeamias.1,3,4 For various types of tumors various levels of nagalase activity were found.7 It seems likely that secretory capacity of individual tumor tissue varies among tumor types depending upon tumor size, staging, and the degree of malignancy or invasiveness.7 Increased nagalase activity has not been detected in the blood of healthy humans.1
It has been established that the nagalase activity is directly proportional to viable tumour burden..1,2 Studies correlating nagalse levels with tumour burden suggest that the measurement of this enzyme can diagnose the presence of cancerous lesions below levels detectable by other diagnostic means.1 In research a day after surgical removal of primary tumours from cancer patients nagalase activity suddenly decreased to near the tumour-free control level, suggesting that the half-life value of nagalse is less than 24 hous.1,6 The short half-life of nagalase is valuable for prognosis of the disease during various therapies.1,5
Nagalase is the intrinsic component of the envelope protein gp120 of HIV-virions and of the envelope protein hemagglutinin (HA) of influenza virus. Nagalase activity is the sum of enzyme activities carried by both HIV virions and unassembled envelope proteins.4
Nagalase in blood is a sensitive test for monitoring the effect of therapy in cancer and certain viral infections, including HIV infection. Because of the short half-life of nagalase, the method is suitable for monitoring various types of therapy. The great sensitivity of the test may help the physician / oncologist in obtaining a better understanding of the therapy and to fine-tune the treatment.
- M Korbelik, VR Naraparaju and N Yamamoto.The value of serum alfa-N-acetylgalactosaminidase measurement for the assessment of tumour response to radio- and photodynamic therapy. British Joumal of Cancer (1998) 77(6), 1009-1014
- Reddi AL et al. Serum alpha-N-acetylgalactosaminidase is associated with diagnosis/prognosis of patients with squamous cell carcinoma of the uterine cervix. Cancer Lett. 2000 Sep 29;158(1):61-4.
- Yamamoto N and Urade M. Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the hemagglutinin of influenza virus..Microbes Infect 2005 Apr;7(4):674-81. Epub 2005 Mar 22.
- Yamamoto N. Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the envelope glycoprotein gp160 of human immunodeficiency virus Type 1. AIDS Res Hum Retroviruses. 2006 Mar;22(3):262-71.
- Yamamoto N. Immunotherpy for prostate cancer with GC Protein-derived macrophage-activating factor, GcMAF. Translational Oncology. Vol 1, no 2 june 2008, [pp 65-72.
- Yamamoto N et al. Therapeutic efficacy of vitamin D3 binding protein derived macrophage activating factor for prostate, breast and colon cancers. Cancer Res. Proc. 38; 31 (1997)
- Yamamoto N et al. Deglycosylation of serum vitamin D3-binding protein leads to immunosuppression in Cancer Patients. Cancer Research 56 : 2827-2831, june 15, 1996.