Glycobiology最新文献

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Enzymatic glycosylation of aloesone performed by plant UDP-dependent glycosyltransferases. 植物 UDP 依赖性糖基转移酶对芦荟酮进行酶糖基化。
IF 3.4 3区 生物学
Glycobiology Pub Date : 2024-07-26 DOI: 10.1093/glycob/cwae050
Natalia Putkaradze, Laura Dato, Onur Kırtel, Jørgen Hansen, Ditte Hededam Welner
{"title":"Enzymatic glycosylation of aloesone performed by plant UDP-dependent glycosyltransferases.","authors":"Natalia Putkaradze, Laura Dato, Onur Kırtel, Jørgen Hansen, Ditte Hededam Welner","doi":"10.1093/glycob/cwae050","DOIUrl":"10.1093/glycob/cwae050","url":null,"abstract":"<p><p>Aloesone is a bioactive natural product and biosynthetic precursor of rare glucosides found in rhubarb and some aloe plants including Aloe vera. This study aimed to investigate biocatalytic aloesone glycosylation and more than 400 uridine diphosphate-dependent glycosyltransferase (UGT) candidates, including multifunctional and promiscuous enzymes from a variety of plant species were assayed. As a result, 137 selective aloesone UGTs were discovered, including four from the natural producer rhubarb. Rhubarb UGT72B49 was further studied and its catalytic constants (kcat = 0.00092 ± 0.00003 s-1, KM = 30 ± 2.5 μM) as well as temperature and pH optima (50 °C and pH 7, respectively) were determined. We further aimed to find an efficient aloesone glycosylating enzyme with potential application for biocatalytic production of the glucoside. We discovered UGT71C1 from Arabidopsis thaliana as an efficient aloesone UGT showing a 167-fold higher catalytic efficiency compared to that of UGT72B49. Interestingly, sequence analysis of all the 137 newly identified aloesone UGTs showed that they belong to different phylogenetic groups, with the highest representation in groups B, D, E, F and L. Finally, our study indicates that aloesone C-glycosylation is highly specific and rare, since it was not possible to achieve in an efficient manner with any of the 422 UGTs assayed, including multifunctional GTs and 28 known C-UGTs.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11273223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141599105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of heparin-binding amino acid residues in antibody HS4C3 with the potential to design antibodies against heparan sulfate domains. 鉴定抗体 HS4C3 中与肝素结合的氨基酸残基,以设计针对硫酸肝素结构域的抗体。
IF 3.4 3区 生物学
Glycobiology Pub Date : 2024-06-22 DOI: 10.1093/glycob/cwae046
Lars A A Damen, Thao P Bui, Thierry van Wessel, Yong Li, Bart F Straten, Robin Pampiermole, Willeke F Daamen, David G Fernig, Toin H van Kuppevelt
{"title":"Identification of heparin-binding amino acid residues in antibody HS4C3 with the potential to design antibodies against heparan sulfate domains.","authors":"Lars A A Damen, Thao P Bui, Thierry van Wessel, Yong Li, Bart F Straten, Robin Pampiermole, Willeke F Daamen, David G Fernig, Toin H van Kuppevelt","doi":"10.1093/glycob/cwae046","DOIUrl":"10.1093/glycob/cwae046","url":null,"abstract":"<p><p>Heparan sulfate (HS) is a linear polysaccharide with high structural and functional diversity. Detection and localization of HS in tissues can be performed using single chain variable fragment (scFv) antibodies. Although several anti-HS antibodies recognizing different sulfation motifs have been identified, little is known about their interaction with HS. In this study the interaction between the scFv antibody HS4C3 and heparin was investigated. Heparin-binding lysine and arginine residues were identified using a protect and label methodology. Site-directed mutagenesis was applied to further identify critical heparin-binding lysine/arginine residues using immunohistochemical and biochemical assays. In addition, computational docking of a heparin tetrasaccharide towards a 3-D homology model of HS4C3 was applied to identify potential heparin-binding sites. Of the 12 lysine and 15 arginine residues within the HS4C3 antibody, 6 and 9, respectively, were identified as heparin-binding. Most of these residues are located within one of the complementarity determining regions (CDR) or in their proximity. All basic amino acid residues in the CDR3 region of the heavy chain were involved in binding. Computational docking showed a heparin tetrasaccharide close to these regions. Mutagenesis of heparin-binding residues reduced or altered reactivity towards HS and heparin. Identification of heparin-binding arginine and lysine residues in HS4C3 allows for better understanding of the interaction with HS and creates a framework to rationally design antibodies targeting specific HS motifs.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inter domain linker region affects properties of CBM6 in GH5_34 arabinoxylanases and alters oligosaccharide product profile. 结构域间连接区影响 GH5_34 阿拉伯木聚糖酶中 CBM6 的特性,并改变寡糖的产物特征。
IF 3.4 3区 生物学
Glycobiology Pub Date : 2024-06-22 DOI: 10.1093/glycob/cwae048
Siri Norlander, Andrius Jasilionis, Leila Allahgholi, Christina Wennerberg, Carl Grey, Patrick Adlercreutz, Eva Nordberg Karlsson
{"title":"Inter domain linker region affects properties of CBM6 in GH5_34 arabinoxylanases and alters oligosaccharide product profile.","authors":"Siri Norlander, Andrius Jasilionis, Leila Allahgholi, Christina Wennerberg, Carl Grey, Patrick Adlercreutz, Eva Nordberg Karlsson","doi":"10.1093/glycob/cwae048","DOIUrl":"10.1093/glycob/cwae048","url":null,"abstract":"<p><p>Understanding the relation between enzyme domain structure and catalytic activity is crucial for optimal engineering of novel enzymes for lignocellulose bioconversion. Xylanases with varying specificities are commonly used to valorise the hemicellulose arabinoxylan (AX), yet characterization of specific arabinoxylanases remain limited. Two homologous GH5_34 arabinoxylanases, HhXyn5A and CtXyn5A, in which the two domains are connected by a 40-residue linker, exhibit distinct activity on AX, yielding different reaction product patterns, despite high sequence identity, conserved active sites and similar domain composition. In this study, the carbohydrate binding module 6 (CBM6), or the inter domain linker together with CBM6, were swapped to investigate their influence on hydrolytic activity and oligosaccharide product pattern on cereal AXs. The variants, with only CBM6 swapped, displayed reduced activity on commercial wheat and rye AX, as well as on extracted oat fibre, compared to the original enzymes. Additionally, exchange of both linker and CBM6 resulted in a reduced ratio of enzyme produced in soluble form in Escherichia coli cultivations, causing loss of activity of both HhXyn5A and CtXyn5A variants. Analysis of oligosaccharide product patterns applying HPAEC-PAD revealed a decreased number of reaction products for CtXyn5A with swapped CBM6, which resembled the product pattern of HhXyn5A. These findings emphasize the importance of the CBM6 interactions with the linker and the catalytic domain for enzyme activity and specificity, and underlines the role of the linker in enzyme structure organisation and product formation, where alterations in linker interactions with the catalytic and/or CBM6 domains, influence enzyme-substrate association and specificity.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of endogenous NOTCH1 from POFUT1 S162L patient fibroblasts reveals the importance of the O-fucose modification on EGF12 in human development. 对来自 POFUT1 S162L 患者成纤维细胞的内源性 NOTCH1 的分析揭示了 EGF12 上的 O 型岩藻糖修饰在人类发育过程中的重要性。
IF 3.4 3区 生物学
Glycobiology Pub Date : 2024-06-22 DOI: 10.1093/glycob/cwae047
Kenjiroo Matsumoto, Kelvin B Luther, Robert S Haltiwanger
{"title":"Analysis of endogenous NOTCH1 from POFUT1 S162L patient fibroblasts reveals the importance of the O-fucose modification on EGF12 in human development.","authors":"Kenjiroo Matsumoto, Kelvin B Luther, Robert S Haltiwanger","doi":"10.1093/glycob/cwae047","DOIUrl":"10.1093/glycob/cwae047","url":null,"abstract":"<p><p>NOTCH1 is a transmembrane receptor interacting with membrane-tethered ligands on opposing cells that mediate the direct cell-cell interaction necessary for many cell fate decisions. Protein O-fucosyltransferase 1 (POFUT1) adds O-fucose to Epidermal Growth Factor (EGF)-like repeats in the NOTCH1 extracellular domain, which is required for trafficking and signaling activation. We previously showed that POFUT1 S162L caused a 90% loss of POFUT1 activity and global developmental defects in a patient; however, the mechanism by which POFUT1 contributes to these symptoms is still unclear. Compared to controls, POFUT1 S162L patient fibroblast cells had an equivalent amount of NOTCH1 on the cell surface but showed a 60% reduction of DLL1 ligand binding and a 70% reduction in JAG1 ligand binding. To determine if the reduction of O-fucose on NOTCH1 in POFUT1 S162L patient fibroblasts was the cause of these effects, we immunopurified endogenous NOTCH1 from control and patient fibroblasts and analyzed O-fucosylation using mass spectral glycoproteomics methods. NOTCH1 EGF8 to EGF12 comprise the ligand binding domain, and O-fucose on EGF8 and EGF12 physically interact with ligands to enhance affinity. Glycoproteomics of NOTCH1 from POFUT1 S162L patient fibroblasts showed WT fucosylation levels at all sites analyzed except for a large decrease at EGF9 and the complete absence of O-fucose at EGF12. Since the loss of O-fucose on EGF12 is known to have significant effects on NOTCH1 activity, this may explain the symptoms observed in the POFUT1 S162L patient.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spatial N-glycomics of the normal breast microenvironment reveals fucosylated and high-mannose N-glycan signatures related to BI-RADS density and ancestry. 正常乳腺微环境的空间 N-聚糖图揭示了与 BIRADS 密度和血统有关的岩藻糖基化和高甘露糖 N-聚糖特征。
IF 3.4 3区 生物学
Glycobiology Pub Date : 2024-06-22 DOI: 10.1093/glycob/cwae043
Denys Rujchanarong, Laura Spruill, George E Sandusky, Yeonhee Park, Anand S Mehta, Richard R Drake, Marvella E Ford, Harikrishna Nakshatri, Peggi M Angel
{"title":"Spatial N-glycomics of the normal breast microenvironment reveals fucosylated and high-mannose N-glycan signatures related to BI-RADS density and ancestry.","authors":"Denys Rujchanarong, Laura Spruill, George E Sandusky, Yeonhee Park, Anand S Mehta, Richard R Drake, Marvella E Ford, Harikrishna Nakshatri, Peggi M Angel","doi":"10.1093/glycob/cwae043","DOIUrl":"10.1093/glycob/cwae043","url":null,"abstract":"<p><p>Higher breast cancer mortality rates continue to disproportionally affect black women (BW) compared to white women (WW). This disparity is largely due to differences in tumor aggressiveness that can be related to distinct ancestry-associated breast tumor microenvironments (TMEs). Yet, characterization of the normal microenvironment (NME) in breast tissue and how they associate with breast cancer risk factors remains unknown. N-glycans, a glucose metabolism-linked post-translational modification, has not been characterized in normal breast tissue. We hypothesized that normal female breast tissue with distinct Breast Imaging and Reporting Data Systems (BI-RADS) categories have unique microenvironments based on N-glycan signatures that varies with genetic ancestries. Profiles of N-glycans were characterized in normal breast tissue from BW (n = 20) and WW (n = 20) at risk for breast cancer using matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). A total of 176 N-glycans (32 core-fucosylated and 144 noncore-fucosylated) were identified in the NME. We found that certain core-fucosylated, outer-arm fucosylated and high-mannose N-glycan structures had specific intensity patterns and histological distributions in the breast NME dependent on BI-RADS densities and ancestry. Normal breast tissue from BW, and not WW, with heterogeneously dense breast densities followed high-mannose patterns as seen in invasive ductal and lobular carcinomas. Lastly, lifestyles factors (e.g. age, menopausal status, Gail score, BMI, BI-RADS) differentially associated with fucosylated and high-mannose N-glycans based on ancestry. This study aims to decipher the molecular signatures in the breast NME from distinct ancestries towards improving the overall disparities in breast cancer burden.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chondroitin sulfate glycan sulfation patterns influence histochemical labeling of perineuronal nets: a comparative study of interregional distribution in human and mouse brain. 硫酸软骨素糖硫酸化模式对神经元周围网组织化学标记的影响:人脑和小鼠大脑区域间分布的比较研究。
IF 3.4 3区 生物学
Glycobiology Pub Date : 2024-06-22 DOI: 10.1093/glycob/cwae049
Claudia Belliveau, Stéphanie Théberge, Stefanie Netto, Reza Rahimian, Gohar Fakhfouri, Clémentine Hosdey, Maria Antonietta Davoli, Aarun Hendrickson, Kathryn Hao, Bruno Giros, Gustavo Turecki, Kimberly M Alonge, Naguib Mechawar
{"title":"Chondroitin sulfate glycan sulfation patterns influence histochemical labeling of perineuronal nets: a comparative study of interregional distribution in human and mouse brain.","authors":"Claudia Belliveau, Stéphanie Théberge, Stefanie Netto, Reza Rahimian, Gohar Fakhfouri, Clémentine Hosdey, Maria Antonietta Davoli, Aarun Hendrickson, Kathryn Hao, Bruno Giros, Gustavo Turecki, Kimberly M Alonge, Naguib Mechawar","doi":"10.1093/glycob/cwae049","DOIUrl":"10.1093/glycob/cwae049","url":null,"abstract":"<p><p>Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns. Literature suggests that CS disaccharide sulfation patterns can influence the function of PNNs as well as their labeling. This study was conducted to characterize such interregional CS disaccharide sulfation pattern differences in adult human (n = 81) and mouse (n = 19) brains. Liquid chromatography tandem mass spectrometry was used to quantify five different CS disaccharide sulfation patterns, which were then compared to immunolabeling of PNNs using Wisteria Floribunda Lectin (WFL) to identify CS-glycosaminoglycans and anti-aggrecan to identify CS proteoglycans. In healthy brains, significant regional and species-specific differences in CS disaccharide sulfation and single versus double-labeling pattern were identified. A secondary analysis to investigate how early-life stress impacts these PNN features discovered that although early-life stress increases WFL+ PNN density, the CS-glycosaminoglycan sulfation code and single versus double PNN-labeling distributions remained unaffected in both species. These results underscore PNN complexity in traditional research, emphasizing the need to consider their heterogeneity in future experiments.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141599104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A hierarchical structure in the N-glycosylation process governs the N-glycosylation output: prolonged cultivation induces glycoenzymes expression variations that are reflected in the cellular N-glycome but not in the protein and site-specific glycoprofile of CHO cells. N-糖基化过程中的分层结构制约着 N-糖基化的产出:长期培养诱导糖酶表达的变化反映在细胞的 N-糖收入中,但不反映在 CHO 细胞的蛋白质和特定位点的糖图谱中。
IF 3.4 3区 生物学
Glycobiology Pub Date : 2024-06-22 DOI: 10.1093/glycob/cwae045
Ilaria Arigoni-Affolter, Marie-Estelle Losfeld, René Hennig, Erdmann Rapp, Markus Aebi
{"title":"A hierarchical structure in the N-glycosylation process governs the N-glycosylation output: prolonged cultivation induces glycoenzymes expression variations that are reflected in the cellular N-glycome but not in the protein and site-specific glycoprofile of CHO cells.","authors":"Ilaria Arigoni-Affolter, Marie-Estelle Losfeld, René Hennig, Erdmann Rapp, Markus Aebi","doi":"10.1093/glycob/cwae045","DOIUrl":"10.1093/glycob/cwae045","url":null,"abstract":"<p><p>N-glycosylation is a central component in the modification of secretory proteins. One characteristic of this process is a heterogeneous output. The heterogeneity is the result of both structural constraints of the glycoprotein as well as the composition of the cellular glycosylation machinery. Empirical data addressing correlations between glycosylation output and glycosylation machinery composition are seldom due to the low abundance of glycoenzymes. We assessed how differences in the glycoenzyme expression affected the N-glycosylation output at a cellular as well as at a protein-specific level. Our results showed that cellular N-glycome changes could be correlated with the variation of glycoenzyme expression, whereas at the protein level differential responses to glycoenzymes alterations were observed. We therefore identified a hierarchical structure in the N-glycosylation process: the enzyme levels in this complex pathway determine its capacity (reflected in the N-glycome), while protein-specific parameters determine the glycosite-specificity. What emerges is a highly variable and adaptable protein modification system that represents a hallmark of eukaryotic cells.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11231950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glyco-Forum. Glyco-Forum.
IF 3.4 3区 生物学
Glycobiology Pub Date : 2024-06-22 DOI: 10.1093/glycob/cwae044
{"title":"Glyco-Forum.","authors":"","doi":"10.1093/glycob/cwae044","DOIUrl":"https://doi.org/10.1093/glycob/cwae044","url":null,"abstract":"","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":"34 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HARRY SCHACHTER obituary. 哈里-夏赫特(HARRY SCHACHTER)讣告。
IF 4.3 3区 生物学
Glycobiology Pub Date : 2024-06-19 DOI: 10.1093/glycob/cwae040
Inka Brockhausen, Jim Dennis, Paul Gleeson, Kelley Moremen, Pamela Stanley
{"title":"HARRY SCHACHTER obituary.","authors":"Inka Brockhausen, Jim Dennis, Paul Gleeson, Kelley Moremen, Pamela Stanley","doi":"10.1093/glycob/cwae040","DOIUrl":"https://doi.org/10.1093/glycob/cwae040","url":null,"abstract":"","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Limited impact of cancer-derived gangliosides on anti-tumor immunity in colorectal cancer. 癌症衍生神经节苷脂对大肠癌抗肿瘤免疫的影响有限。
IF 3.4 3区 生物学
Glycobiology Pub Date : 2024-05-26 DOI: 10.1093/glycob/cwae036
Irene van der Haar Àvila, Tao Zhang, Victor Lorrain, Florance de Bruin, Tianne Spreij, Hitoshi Nakayama, Kazuhisa Iwabuchi, Juan J García-Vallejo, Manfred Wuhrer, Yvette van Kooyk, Sandra J van Vliet
{"title":"Limited impact of cancer-derived gangliosides on anti-tumor immunity in colorectal cancer.","authors":"Irene van der Haar Àvila, Tao Zhang, Victor Lorrain, Florance de Bruin, Tianne Spreij, Hitoshi Nakayama, Kazuhisa Iwabuchi, Juan J García-Vallejo, Manfred Wuhrer, Yvette van Kooyk, Sandra J van Vliet","doi":"10.1093/glycob/cwae036","DOIUrl":"10.1093/glycob/cwae036","url":null,"abstract":"<p><p>Aberrant glycosylation is a key mechanism employed by cancer cells to evade immune surveillance, induce angiogenesis and metastasis, among other hallmarks of cancer. Sialic acids, distinctive terminal glycan structures located on glycoproteins or glycolipids, are prominently upregulated across various tumor types, including colorectal cancer (CRC). Sialylated glycans modulate anti-tumor immune responses through their interactions with Siglecs, a family of glycan-binding receptors with specificity for sialic acid-containing glycoconjugates, often resulting in immunosuppression. In this paper, we investigated the immunomodulatory function of ST3Gal5, a sialyltransferase that catalyzes the addition of α2-3 sialic acids to glycosphingolipids, since lower expression of ST3Gal5 is associated with better survival of CRC patients. We employed CRISPR/Cas9 to knock out the ST3Gal5 gene in two murine CRC cell lines MC38 and CT26. Glycomics analysis confirmed the removal of sialic acids on glycolipids, with no discernible impact on glycoprotein sialylation. Although knocking out ST3Gal5 in both cell lines did not affect in vivo tumor growth, we observed enhanced levels of regulatory T cells in CT26 tumors lacking ST3Gal5. Moreover, we demonstrate that the absence of ST3Gal5 affected size and blood vessel density only in MC38 tumors. In summary, we ascertain that sialylation of glycosphingolipids has a limited influence on the anti-tumor immune response in CRC, despite detecting alterations in the tumor microenvironment, possibly due to a shift in ganglioside abundance.</p>","PeriodicalId":12766,"journal":{"name":"Glycobiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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