Therapeutic intervention with complement and complement receptors in cancer

Ross, Gordon D.; Yan, Jun; Větvička, Václav; Xia, Yu; Hanikýřová, M.; Carroll, M C; Mayadas, Tanya N.

doi:10.1016/s0161-5890(98)90790-8

Cited by 4 publications

(4 citation statements)

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“…The identity of the ␤ -glucan receptor, which has been defined as a ␤ -glucan inhibitable receptor for particulate activators of the alternative complement pathway (6), is controversial. The ability of CR3 to recognize ␤ -glucans led to the proposal that this receptor is the major ␤ -glucan receptor on leukocytes and that it mediates all the immunomodulatory effects of these carbohydrates, including the ␤ -glucan-dependent binding of zymosan (4,(9)(10)(11). Conflicting evidence, however, indicated that another receptor(s) mediates this activity (6,(12)(13)(14), and although we and others have identified additional receptors capable of recognizing ␤ -glucans (15)(16)(17), their role in primary cells is unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Zymosan is a yeast-derived particle composed principally of polysaccharides, of which ␤ -glucan, the active component mediating the cellular effects (2), and mannan are the major constituents (3). In vivo administration of zymosan, or purified soluble ␤ -glucans, has a number of desirable effects on immune function, including the ability to confer resistance to tumors and various infections, prompting interest in the development of ␤ -glucanbased therapeutics (4,5). Despite the significant therapeutic implications, the molecular mechanism through which these effects are mediated is not known.…”

Section: Introductionmentioning

confidence: 99%

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Dectin-1 Is A Major β-Glucan Receptor On Macrophages

Brown

Taylor

Reid

et al. 2002

The Journal of Experimental Medicine

904

704

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Zymosan is a β-glucan– and mannan-rich particle that is widely used as a cellular activator for examining the numerous responses effected by phagocytes. The macrophage mannose receptor (MR) and complement receptor 3 (CR3) have historically been considered the major macrophage lectins involved in the nonopsonic recognition of these yeast-derived particles. Using specific carbohydrate inhibitors, we show that a β-glucan receptor, but not the MR, is a predominant receptor involved in this process. Furthermore, nonopsonic zymosan binding was unaffected by genetic CD11b deficiency or a blocking monoclonal antibody (mAb) against CR3, demonstrating that CR3 was not the β-glucan receptor mediating this activity. To address the role of the recently described β-glucan receptor, Dectin-1, we generated a novel anti–Dectin-1 mAb, 2A11. Using this mAb, we show here that Dectin-1 was almost exclusively responsible for the β-glucan–dependent, nonopsonic recognition of zymosan by primary macro-phages. These findings define Dectin-1 as the leukocyte β-glucan receptor, first described over 50 years ago, and resolves the long-standing controversy regarding the identity of this important molecule. Furthermore, these results identify Dectin-1 as a new target for examining the immunomodulatory properties of β-glucans for therapeutic drug design.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dectin-1 Is A Major β-Glucan Receptor On Macrophages

Brown

Taylor

Reid

et al. 2002

The Journal of Experimental Medicine

904

704

View full text Add to dashboard Cite

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“…The C3b cleavage fragment (iC3b) serves as a receptor of natural killer (NK) cells, which are the most potent, tumoreliminating, immune weapon of the host. MT1-MMP, by shedding iC3b from the cell surface, interferes with anticancer cellular immunity (23). Consequently, MT1-MMP inhibits the complement cascade and protects tumor cells from complement-mediated injury.…”

Section: Introductionmentioning

confidence: 99%

Interference with the Complement System by Tumor Cell Membrane Type-1 Matrix Metalloproteinase Plays a Significant Role in Promoting Metastasis in Mice

Rozanov¹,

Savinov²,

Golubkov³

et al. 2006

Cancer Research

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Neoplasms have developed strategies to protect themselves against the complement-mediated host immunity. Invasionand metastasis-promoting membrane type-1 (MT1) matrix metalloproteinase (MMP) is strongly associated with many metastatic cancer types. The relative importance of the individual functions of MT1-MMP in metastasis was, however, unknown. We have now determined that the expression of murine MT1-MMP in murine melanoma B16F1 cells strongly increased the number of metastatic loci in the lungs of syngeneic C57BL/6 mice. In contrast, MT1-MMP did not affect the number of metastatic loci in complement-deficient C57BL/6-C3 À/À mice. Our results indicated, for the first time, that the anticomplement activity of MT1-MMP played a significant role in promoting metastasis in vivo and determined the relative importance of the anticomplement activity in the total metastatic effect of this multifunctional proteolytic enzyme. We believe that our results shed additional light on the functions of MT1-MMP in cancer and clearly make this protease a promising drug target in metastatic malignancies.

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“…β-1,3/1,6-D-glucan obtained from the yeast is known as a natural immunostimulant. β-D-glucans affect selected receptors that among others include CD11b/CD18 (CR3), lactosylceramide, scavenger receptors and TLR2 (toll-like receptor 3), TLR4 by activating macrophages, phagocytes and T-helper lymphocytes (Ross et al 1999). They stimulate phagocytes for the production of cytokines IL-1, IL-9, TNF-α, as well as affect the synthesis of acute-phase proteins, including ceruloplasmin .…”

mentioning

confidence: 99%

Effect of β-1,3/1,6-D-glucan in diet on productivity and humoral and cellular defense mechanisms in sheep

et al. 2013

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The aim of this study was to determine the effect of β-1,3/1,6-D-glucan, isolated from Saccharomyces cerevisiae, on indicators of milk and meat performance in sheep as well as on selected non-specific indicators of humoral and cellular defense. The experiment was carried on 26 suckling ewes divided into 2 equal groups, and their offspring (21 in each group). The ewes were administered concentrate with the addition of β-1,3/1,6-D-glucan at a dose of 3 g/kg. Indicators of milk performance and markers of humoral and cellular immunity were analyzed on days 28 and 70 of lactation; and the indicators of meat performance of lambs on day 28 and 70 of their life. The addition of β-1,3/1,6-D-glucan was observed to cause an increase in milk performance by 13.5-14%. Simultaneously, milk was characterized by a lower somatic cell count. Diet supplementation had a positive effect on the chemical composition of milk, which was manifested by increased percentage contents of fat (by 15-30%) and protein (by 11%). Lambs were characterized by a higher growth rate and better muscle tissue development. The supplementation caused an increase of gamma-globulin concentration (by 6.33-9.5 g/l), lysozyme activity (by 0.1 mg/l), respiratory burst activity (by 0.11-0.14), potential killing activity (by 0.10-0.12), proliferative response of T-cells stimulated by mitogen concanavalineA (by 0.07-0.09 RI) and proliferative response of B-cells stimulated by mitogen lipopolysaccharide (by 0.13-0.16 RI) in sheep's blood. The activity of β-1,3/1,6-D-glucan as a natural immunostimulator has been studied in many animal species, however, this is the first study conducted on sheep. Milk yield and composition, musculus longissiumus dorsi, ultrasound scanning, anti-infective immunity

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Therapeutic intervention with complement and complement receptors in cancer

Cited by 4 publications

References 0 publications

Dectin-1 Is A Major β-Glucan Receptor On Macrophages

Dectin-1 Is A Major β-Glucan Receptor On Macrophages

Interference with the Complement System by Tumor Cell Membrane Type-1 Matrix Metalloproteinase Plays a Significant Role in Promoting Metastasis in Mice

Effect of β-1,3/1,6-D-glucan in diet on productivity and humoral and cellular defense mechanisms in sheep

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