Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes

Abstract

Carbohydrate-based vaccines have shown therapeutic efficacy for infectious disease and cancer. The mushroom Ganoderma lucidum (Reishi) containing complex polysaccharides has been used as antitumor supplement, but the mechanism of immune response has rarely been studied. Here, we show that the mice immunized with a L-fucose (Fuc)-enriched Reishi polysaccharide fraction (designated as FMS) induce antibodies against murine Lewis lung carcinoma cells, with increased antibody-mediated cytotoxicity and reduced production of tumor-associated inflammatory mediators (in particular, monocyte chemoattractant protein-1). The mice showed a significant increase in the peritoneal B1 B-cell population, suggesting FMS-mediated anti-glycan IgM production. Furthermore, the glycan microarray analysis of FMS-induced antisera displayed a high specificity toward tumor-associated glycans, with the antigenic structure located in the nonreducing termini (i.e., Fucα1-2Galβ1-3GalNAc-R, where Gal, GalNAc, and R represent, respectively, Dgalactose, D-N-acetyl galactosamine, and reducing end), typically found in Globo H and related tumor antigens. The composition of FMS contains mainly the backbone of 1,4-mannan and 1,6-α-galactan and through the Fucα1-2Gal, Fucα1-3/4Man, Fucα1-4Xyl, and Fucα1-2Fuc linkages (where Man and Xyl represent D-mannose and D-xylose, respectively), underlying the molecular basis of the FMSinduced IgM antibodies against tumor-specific glycans. mushroom polysaccharide | antitumor activity | anti-Globo H antibody V arious forms of herbal medicine polysaccharides have become valuable as health supplements worldwide (1, 2), suggesting that administration of such polysaccharides may improve innate immunity in vivo. The underlying molecular mechanisms, however, still remain ambiguous. Aberrant terminal fucosylation as well as sialylation in tumor-associated glycans is one of several glycosylation events important in cancer progression (3, 4), and such unusual glycans have recently been used for the development of anticancer vaccines (5-7). As an example, the Globo H-based glycoconjugate vaccines are currently undergoing large-scale clinical trials and have shown promise in therapeutic treatment (8, 9). Studies on the immune response to pathogenic microorganisms (such as Haemophilus influenza type B and Streptococcus pneumonia) have demonstrated that polysaccharides containing repeating antigenic units are generally T cell-independent (TI) (10, 11). Furthermore, recent findings revealed that specific B-cell subsets could establish memory for providing specific Ig synthesis in response to TI-associated polysaccharides (12)(13)(14). In an attempt to understand the biological significance of polysaccharides derived from natural sources, we previously isolated and characterized a crude extract fraction of water-soluble and L-fucose (Fuc)-containing polysaccharides (F3) from Ganoderma lucidum (Reishi) (a mushroom that has been long used as a herb medicine) (15). F3 has since been shown essential for regulation of cytokine network...

Chemical features of Ganoderma polysaccharides with antioxidant, antitumor and antimicrobial activities

“…Different studies showed that bioactive polysaccharides and extracts could stimulate blood mononuclear cells to increase cytokines, tumor necrosis factor, interferon and interleukins production, induce apoptosis and meaningfully increased the lifespan of the tumor-implanted mice (Paterson, 2006;Ramberg et al, 2010;Roupas et al, 2010;Liao et al, 2013).…”

Free sugar, amino acid, and beta-glucan content in Lentinula edodes strains collected from different areas

“…버섯의 항산화 활성에는 유리당이 상당 부분 관여한다는 기존 보고가 있 었으며, fucose는 항산화활성을 나타내는 대표적 유리당 으로 알려져 있다 (Liao et al, 2013). 이러한 결과를 기초 Total amino acid.…”

A comparison of the gene expression profiles and pathway network analyses after treatment of Prostate cancer cell lines with different Ganoderma lucidum based extracts

“…Several studies have shown that Ganoderma polysaccharides can exert their anti-cancer activity via stimulating the host's immune system [16,66,67]. However, as there are no immune cells present in cell culture, changes in immune activity does not explain the observed growth inhibition in IC 50 cell line studies.…”