Differences in the sialylation patterns of membrane stress proteins in chemical carcinogen-induced tumors developed in BALB/c and IL-1α deficient mice

Avidan, Avi; Perlmutter, Michal; Tal, Smadar; Oraki, Omer; Kapp, Tsachi; Krelin, Yacov; Elkabets, Moshe; Dotan, Shahar; Apte, Ron N.; Lichtenstein, Rachel G.

doi:10.1007/s10719-009-9238-9

Cited by 12 publications

(15 citation statements)

References 39 publications

(45 reference statements)

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“…mice, we detected lower expression of a2-6 sialyltransferase, compared with MCA-induced lines derived from WT mice, which corroborates the results of Avidan et al (19). Our data suggest that sialylation of the tumor cell surface or sialylation of specific moieties determines the differential ability to stimulate different immune responses.…”

Section: Discussionsupporting

confidence: 91%

“…The renewal of sialic acid levels to the original status was examined in sialidase-treated WT and IL-1a 2/2 fibrosarcoma cell lines. According to our previous study, MCAinduced fibrosarcoma cell lines derived from IL-1a 2/2 mice express lower amounts of a2-6 sialyltransferase (ST6GalI) compared with fibrosarcoma cells derived from naive BALB/c mice (19). Therefore, the recovery of sialic acids on IL-1a 2/2 tumor cells was also 50% lower than sialic acid recovery on fibrosarcoma cell lines derived from BALB/c mice at the same time (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 89%

“…We have shown previously that tumors induced by the carcinogen 3-methylcholanthrene (MCA) in IL-1a-deficient mice were not properly edited and were thus highly immunogenic and nontumorigenic in intact mice, as compared with MCA-induced fibrosarcoma cells derived from wild type (WT) BALB/c mice (18). Surface sialylation levels and expression patterns of a2-6 sialyltransferase were lower in cell lines derived from IL-1a 2/2 mice than in cell lines derived from WT mice (19). This finding was also shown to be valid for cell lines derived from MCA-induced fibrosarcoma cells from IFN-g 2/2 mice, because IFN-g is a key component of the cancer immunoediting process (20).…”

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confidence: 99%

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Sialylation of 3-Methylcholanthrene–Induced Fibrosarcoma Determines Antitumor Immune Responses during Immunoediting

Cohen

Elkabets

Perlmutter³

et al. 2010

The Journal of Immunology

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Sialylation of tumor cells is involved in various aspects of their malignancy (proliferation, motility, invasion, and metastasis); however, its effect on the process of immunoediting that affects tumor cell immunogenicity has not been studied. We have shown that in mice with impaired immunoediting, such as in IL-1α−/− and IFNγ−/− mice, 3-methylcholanthrene–induced fibrosarcoma cells are immunogenic and concomitantly bear low levels of surface sialylation, whereas tumor cells derived from wild type mice are nonimmunogenic and bear higher levels of surface sialylation. To study immune mechanisms whose interaction with tumor cells involves surface sialic acid residues, we used highly sialylated 3-methylcholanthrene–induced nonimmunogenic fibrosarcoma cell lines from wild type mice, which were treated with sialidase to mimic immunogenic tumor cell variants. In vivo and in vitro experiments revealed that desialylation of tumor cells reduced their growth and induced cytotoxicity by NK cells. Moreover, sialidase-treated tumor cells better activated NK cells for IFN-γ secretion. The NKG2D-activating receptor on NK cells was shown to be involved in interactions with desialylated ligands on tumor cells, the nature of which is still not known. Thus, the degree of sialylation on tumor cells, which is selected during the process of immunoediting, has possibly evolved as an important mechanism of tumor cells with low intrinsic immunogenicity or select for tumor cells that can evade the immune system or subvert its function. When immunoediting is impaired, such as in IFN-γ−/− and IL-1α−/− mice, the overt tumor consists of desialylayed tumor cells that interact better with immunosurveillance cells.

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Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 89%

mentioning

confidence: 99%

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Sialylation of 3-Methylcholanthrene–Induced Fibrosarcoma Determines Antitumor Immune Responses during Immunoediting

Cohen

Elkabets

Perlmutter³

et al. 2010

The Journal of Immunology

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“…The gels were run in a MiniProtean3 device (Bio-Rad) for 75 min at 140–170 mV, at a current lower than 350 mA [18]. The IgG molecules were visualized with Coomassie blue stain and the relevant bands were excised, cut into small pieces and dried using vacuum centrifugation.…”

Section: Methodsmentioning

confidence: 99%

Glycans in Sera of Amyotrophic Lateral Sclerosis Patients and Their Role in Killing Neuronal Cells

et al. 2012

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by degeneration of upper and lower motor neurons. To date, glycosylation patterns of glycoproteins in fluids of ALS patients have not been described. Moreover, the aberrant glycosylation related to the pathogenesis of other neurodegenerative diseases encouraged us to explore the glycome of ALS patient sera. We found high levels of sialylated glycans and low levels of core fucosylated glycans in serum-derived N-glycans of patients with ALS, compared to healthy volunteer sera. Based on these results, we analyzed the IgG Fc N297-glycans, as IgG are major serum glycoproteins affected by sialylation or core fucosylation and are found in the motor cortex of ALS patients. The analyses revealed a distinct glycan, A2BG2, in IgG derived from ALS patient sera (ALS-IgG). This glycan increases the affinity of IgG to CD16 on effector cells, consequently enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC). Therefore, we explore whether the Fc-N297-glycans of IgG may be involved in ALS disease. Immunostaining of brain and spinal cord tissues revealed over-expression of CD16 and co-localization of intact ALS-IgG with CD16 and in brain with activated microglia of G93A-SOD1 mice. Intact ALS-IgG enhanced effector cell activation and ADCC reaction in comparison to sugar-depleted or control IgG. ALS-IgG were localized in the synapse between brain microglia and neurons of G93A-SOD1 mice, manifesting a promising in vivo ADCC reaction. Therefore, glycans of ALS-IgG may serve as a biomarker for the disease and may be involved in neuronal damage.

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“…Another line of evidence indicating the importance of sialylation in tumor immunology is a recent study in the methylcholanthrene induced fibrosarcoma model (199,200). It was observed that methylcholanthrene induced fibrosarcomas grown in immunecompetent mice expressed high levels of sialic acid on their cell surface.…”

Section: Sialylated N-linked or O-linked Glycans-sialylation Of Glycomentioning

confidence: 99%

The immunomodulating roles of glycoproteins in epithelial ovarian cancer

Felder¹

2012

Front Biosci

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The complexity of the immune system demands an intricate defense mechanism by tumors. Ovarian and other tumors employ specific glycoproteins and the associated glycan sequences to modulate immune responses. Glycoproteins enable tumor cells that express or secrete these molecules to evade immune cell attack and induce the immune system to promote tumor growth. This review focuses first on the immune environment in ovarian cancer, and the mechanisms of activation and inhibition that immune cells undergo in order to either attack or ignore a target cell. Next we illustrate the immunomodulatory roles of ovarian cancer-associated glycans and glycoproteins in 1. preventing immune synapse formation, 2. serving as ligands of immune cell receptors, 3. scavenging cytokines and chemokines, and 4. participating in the formation of autoantibodies against the tumor. The importance of these immunomodulating strategies from the view points of understanding the tumor immunology of ovarian tumors, potential origin of such mechanisms, and specific strategies to circumvent the glycoconjugate-mediated suppression of immune responses is discussed in this review. KeywordsGlycoproteins; T cells; NK cells; Epithelia Ovarian Cancer; MUC16; Glycodelin; MUC1; Mucins; Immune Synapse; Review INTRODUCTIONOvarian cancer is a highly insidious disease that is usually detected at a very late stage when the possibility of an efficient therapeutic management of the cancer is relatively low (1-3). Therefore, in most women with advanced ovarian cancer the five year survival rate is around 30-55% (4). Specific biomarkers that can detect the cancer at an early stage (when the survival rate after treatment is 80%) are not available (5,6). In women with advanced disease, the standard of care includes an initial surgical debulking of the tumor followed by an intense chemotherapy with platinum or taxol based compounds. Under these treatment conditions the cancer regresses and the low level of the tumor is monitored by measuring the Send correspondence to: Manish S. Patankar, Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 600 Highland Avenue, H4/657 CSC, Madison, patankar@wisc.edu. NIH Public Access Author ManuscriptFront Biosci (Elite Ed). Author manuscript; available in PMC 2015 February 12. Published in final edited form as:Front Biosci (Elite Ed). ; 4: 631-650. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript serum concentration of the biomarker CA125 (7-10). A steady elevation in serum CA125 levels from this nadir is indicative of recurrent disease (10).The progression of ovarian cancer requires the cancer cells to first develop on the surface of the ovary or along the walls of the fallopian tubes and then metastasize to other sites within the peritoneum (11)(12)(13)(14)(15)(16)(17)(18). Starting with the initiation of the cancer to metastasis, the tumor cells encounter distinct immunologic environments and therefore have to adapt at each site to not only overcome immune recognition but al...

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Differences in the sialylation patterns of membrane stress proteins in chemical carcinogen-induced tumors developed in BALB/c and IL-1α deficient mice

Cited by 12 publications

References 39 publications

Sialylation of 3-Methylcholanthrene–Induced Fibrosarcoma Determines Antitumor Immune Responses during Immunoediting

Sialylation of 3-Methylcholanthrene–Induced Fibrosarcoma Determines Antitumor Immune Responses during Immunoediting

Glycans in Sera of Amyotrophic Lateral Sclerosis Patients and Their Role in Killing Neuronal Cells

The immunomodulating roles of glycoproteins in epithelial ovarian cancer

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