Analysis of the Biological Properties of Blood Plasma Protein with GcMAF Functional Activity

• Published in: International journal of molecular sciences Vol. 23; no. 15; p. 8075
• Main Authors: Dolgova, Evgeniya V, Kirikovich, Svetlana S, Levites, Evgeniy V, Ruzanova, Vera S, Proskurina, Anastasia S, Ritter, Genrikh S, Taranov, Oleg S, Varaksin, Nikolay A, Ryabicheva, Tatiana G, Leplina, Olga Yu, Ostanin, Alexandr A, Chernykh, Elena R, Bogachev, Sergey S
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-07-2022; MDPI
• Subjects: Actin; Affinity chromatography; Animals; Antitumor activity; Biological properties; Blood cells; Blood plasma; Blood Proteins - metabolism; Cancer therapies; Carcinoma - drug therapy; Cell activation; Cell cycle; Cellular biology; Chemical compounds; Chemotherapy; Clinical medicine; Column chromatography; Cytokines; Deglycosylation; Dendritic cells; Genotype & phenotype; group-specific component protein-derived macrophage-activating factor; Humans; Immune response (humoral); Immune system; Inflammation; Laboratories; Lewis carcinoma; Lymphocytes; M1/M2 macrophages; Macrophage Activation; Macrophage-activating factor; Macrophage-Activating Factors - metabolism; Macrophages; Mice; Pharmacology; Proteins; Stem cells; Stroma; Tumors; Vitamin D-Binding Protein - metabolism; Vitamin D3; vitamin D3 binding protein; Lewis carcinoma; vitamin D3 binding protein; group-specific component protein-derived macrophage-activating factor; M1/M2 macrophages
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23158075

The main problem related to the studies focusing on group-specific component protein-derived macrophage-activating factor (GcMAF) is the lack of clarity about changes occurring in different types of macrophages and related changes in their properties under the effect of GcMAF in various clinical conditions. We analyzed the antitumor therapeutic properties of GcMAF in a Lewis carcinoma model in two clinical conditions: untreated tumor lesion and tumor resorption after exposure to Karanahan therapy. GcMAF is formed during site-specific deglycosylation of vitamin D3 binding protein (DBP). DBP was obtained from the blood of healthy donors using affinity chromatography on a column with covalently bound actin. GcMAF-related factor (GcMAF-RF) was converted in a mixture with induced lymphocytes through the cellular enzymatic pathway. The obtained GcMAF-RF activates murine peritoneal macrophages (p < 0.05), induces functional properties of dendritic cells (p < 0.05) and promotes in vitro polarization of human M0 macrophages to M1 macrophages (p < 0.01). Treatment of whole blood cells with GcMAF-RF results in active production of both pro- and anti-inflammatory cytokines. It is shown that macrophage activation by GcMAF-RF is inhibited by tumor-secreted factors. In order to identify the specific antitumor effect of GcMAF-RF-activated macrophages, an approach to primary reduction of humoral suppressor activity of the tumor using the Karanahan therapy followed by macrophage activation in the tumor-associated stroma (TAS) was proposed. A prominent additive effect of GcMAF-RF, which enhances the primary immune response activation by the Karanahan therapy, was shown in the model of murine Lewis carcinoma. Inhibition of the suppressive effect of TAS is the main condition required for the manifestation of the antitumor effect of GcMAF-RF. When properly applied in combination with any chemotherapy, significantly reducing the humoral immune response at the advanced tumor site, GcMAF-RF is a promising antitumor therapeutic agent that additively destroys the pro-tumor properties of macrophages of the tumor stroma.