Ball Glycosylation and Cancer

1. Auflage 2015
ISBN: 978-0-12-801614-5
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band Volume 126, 418 Seiten

Reihe: Advances in Cancer Research

Advances in Cancer Research provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics. - Provides information on cancer research - Outstanding and original reviews - Suitable for researchers and students

Autoren/Hrsg.

Ball, Lauren

Inhaltsverzeichnis

1;Front Cover;1
2;Glycosylation and Cancer;4
3;Copyright;5
4;Contents;6
5;Contributors;10
6;Preface;14
7;Chapter 1: Glycosylation and Cancer: Moving Glycomics to the Forefront;16
7.1;1. Introduction;16
7.2;2. Contributions to the Volume;17
7.3;3. Opportunities and Challenges;19
7.4;4. Emerging Areas;21
7.5;References;23
8;Chapter 2: Glycans and Cancer: Role of N-Glycans in Cancer Biomarker, Progression and Metastasis, and Therapeutics;26
8.1;1. Introduction;27
8.2;2. Metabolic Pathway of Branched N-Glycans and Their Corresponding Glycosyltransferases;28
8.2.1;2.1. Fut8 (FUT8, Fut8);30
8.2.1.1;2.1.1. Enzymatic properties and gene regulation;30
8.2.1.2;2.1.2. Biological significance and implication in cancer;31
8.2.2;2.2. GnT-III (MGAT3, Mgat3);33
8.2.2.1;2.2.1. Enzymatic properties and gene regulation;33
8.2.2.2;2.2.2. Biological aspects and implication in cancer;35
8.2.3;2.3. GnT-V (MGAT5, Mgat5);36
8.2.3.1;2.3.1. Enzymatic properties and gene regulation;36
8.2.3.2;2.3.2. Biological aspects and implications in cancer;38
8.2.4;2.4. GnT-IVa and GnT-IVb (MGAT4A and MGAT4B, Mgat4a and Mgat4b);43
8.2.4.1;2.4.1. Enzymatic properties and gene regulation;43
8.2.4.2;2.4.2. Biological aspects and implication in cancer;44
8.2.5;2.5. GnT-IX (GnT-Vb or MGAT5B, Mgat5b);47
8.2.5.1;2.5.1. Enzymatic properties and gene regulation;47
8.2.5.2;2.5.2. Biological aspects and implications in cancer;49
8.3;3. Future Perspectives;51
8.3.1;3.1. Disease mechanism;51
8.3.2;3.2. Biomarker discovery;52
8.3.3;3.3. Glycan-based therapeutics;52
8.4;Acknowledgments;54
8.5;References;54
9;Chapter 3: Simple Sugars to Complex Disease-Mucin-Type O-Glycans in Cancer;68
9.1;1. Introduction;69
9.2;2. O-glycan Biosynthesis;74
9.2.1;2.1. Core structures 1-4;76
9.2.2;2.2. Extended O-glycans;79
9.2.3;2.3. Extended core 1;80
9.2.4;2.4. Extended core 2;80
9.2.5;2.5. Extended core 3, 4;81
9.2.6;2.6. ABO blood group antigens;81
9.2.7;2.7. Lewis antigens;83
9.2.8;2.8. Sialic acids;84
9.2.9;2.9. Monosaccharide modifications;85
9.3;3. Altered O-Glycan Structures Observed in Cancer;85
9.3.1;3.1. Methods to identify altered O-glycosylation in cancer;86
9.3.2;3.2. Truncated O-glycans;87
9.3.2.1;3.2.1. Tn antigen;101
9.3.2.1.1;3.2.1.1. Background;101
9.3.2.1.2;3.2.1.2. Histology;101
9.3.2.1.3;3.2.1.3. Mechanisms for expression;102
9.3.2.2;3.2.2. Sialyl-Tn;103
9.3.2.2.1;3.2.2.1. Background;103
9.3.2.2.2;3.2.2.2. Histology;103
9.3.2.2.3;3.2.2.3. Mechanisms for expression;104
9.3.2.3;3.2.3. T antigen;104
9.3.2.3.1;3.2.3.1. Background;104
9.3.2.3.2;3.2.3.2. Histology;105
9.3.2.3.3;3.2.3.3. Mechanisms for expression;105
9.3.2.4;3.2.4. Comparing Tn, STn, and T expression and function in tumor biology;106
9.3.2.4.1;3.2.4.1. Expression;106
9.3.2.4.2;3.2.4.2. Function;106
9.3.3;3.3. Altered terminal and extended structures;107
9.3.3.1;3.3.1. Terminal a-GlcNAc on core 2;107
9.3.3.2;3.3.2. Lewis antigens;115
9.3.3.2.1;3.3.2.1. Background;115
9.3.3.2.2;3.3.2.2. SLea;116
9.3.3.2.3;3.3.2.3. SLex;116
9.3.3.2.4;3.3.2.4. Functions of SLex and SLea in tumor biology;116
9.3.3.2.5;3.3.2.5. Mechanisms for overexpression;117
9.3.3.3;3.3.3. ABH structures;117
9.3.3.3.1;3.3.3.1. Background;117
9.3.3.3.2;3.3.3.2. Histology;117
9.3.3.3.3;3.3.3.3. Mechanisms for altered expression;118
9.3.3.3.4;3.3.3.4. Function of blood group structures in tumor biology;118
9.3.4;3.4. Genetic associations with glycogenes and cancer;119
9.3.5;3.5. Mucins;119
9.4;4. Clinical Applications;120
9.4.1;4.1. Cancer detection;121
9.4.1.1;4.1.1. Serum biomarkers;121
9.4.1.2;4.1.2. Imaging;122
9.4.1.3;4.1.3. Assessing anti-O-glycan immune responses;126
9.4.2;4.2. Cancer therapeutics;127
9.4.2.1;4.2.1. Passive immunotherapies;127
9.4.2.2;4.2.2. Therapeutic vaccines;128
9.4.2.3;4.2.3. Selectin-Lewis interactions;129
9.5;5. Conclusions;130
9.6;Acknowledgments;131
9.7;References;131
10;Chapter 4: Intracellular Protein O-GlcNAc Modification Integrates Nutrient Status with Transcriptional and Metabolic Regu...;152
10.1;1. O-GlcNAc Modification: An Overview;153
10.2;2. Hyper O-GlcNAc Modification Observed in Human Tumors;154
10.3;3. O-GlcNAc Transferase: Structure, Activity, and Regulation;155
10.4;4. O-GlcNAcase: Structure and Function;159
10.5;5. The Hexosamine Biosynthetic Pathway;161
10.6;6. Effects of O-GlcNAc Modification on Epigenetic Regulation;165
10.7;7. Anticancer Effects of Reducing Hyper-O-GlcNAcylation in Cancer Cells;166
10.8;8. Effects of O-GlcNAc Cycling Enzymes on Glucose Homeostasis and Metabolism;167
10.9;9. Detection of O-GlcNAcylated Proteins;169
10.10;10. Conclusions;170
10.11;References;170
11;Chapter 5: The Detection and Discovery of Glycan Motifs in Biological Samples Using Lectins and Antibodies: New Methods a...;182
11.1;1. Introduction;183
11.2;2. Ways to Use GBPs for Probing Glycan Motifs;184
11.2.1;2.1. The detection of glycan motifs;184
11.2.2;2.2. Histochemistry;185
11.2.3;2.3. Imaging;186
11.2.4;2.4. Lectin affinity capture;187
11.2.5;2.5. Antibody-lectin sandwich assays;187
11.2.6;2.6. Lectin arrays;189
11.3;3. Defining the Fine Specificities of GBPs from Glycan Array Data;191
11.3.1;3.1. Need for the expansion of glycan arrays;194
11.4;4. Higher Order Influences on GBP Binding: Density, Location, and Accessibility;196
11.4.1;4.1. Density;196
11.4.2;4.2. Location of a motif within a glycan;197
11.5;5. Quantitative Interpretation of GBP Measurements;198
11.5.1;5.1. Linking with MS data;202
11.6;6. Finding the Right Reagent: Mining Glycan Array Data, Engineering GBPs, and Creating Antibodies;202
11.6.1;6.1. Mining glycan array data;202
11.6.2;6.2. Engineering GBPs;205
11.6.3;6.3. Raising antibodies to specific glycans;206
11.7;7. Discovering Glycan Motifs Using GBPs: Application to Cancer Biomarkers;207
11.7.1;7.1. Discovery by antibody generation;207
11.7.2;7.2. Screening candidates;208
11.8;8. Conclusions and Prospects;209
11.9;References;210
12;Chapter 6: Glycosylation Characteristics of Colorectal Cancer;218
12.1;1. Introduction;219
12.2;2. Changes of Cellular and Tissue Glycosylation in CRC;221
12.2.1;2.1. N-glycans;221
12.2.2;2.2. O-glycans;225
12.2.3;2.3. GSL-glycans;227
12.2.4;2.4. Fucosylation;229
12.2.5;2.5. Sialylation;229
12.2.6;2.6. (Sialyl) Lewis antigens;232
12.2.7;2.7. Sulfation;233
12.2.8;2.8. Conclusion;234
12.3;3. Serum-Related Glycosylation Changes in CRC;235
12.4;4. Biological Relevance of Glycan in CRC;236
12.4.1;4.1. Tumorigenesis;236
12.4.2;4.2. Metastasis;238
12.4.3;4.3. Modulation of immunity;241
12.4.4;4.4. Resistance to therapy;244
12.5;5. Analysis of Glycans: Useful Techniques for Glycomics;244
12.5.1;5.1. Binding assays;245
12.5.2;5.2. Mass spectrometry;246
12.6;6. Conclusion and Future Perspectives;250
12.7;Acknowledgment;252
12.8;References;252
13;Chapter 7: Glycosylation and Liver Cancer;272
13.1;1. Hepatocellular Carcinoma;273
13.2;2. Hepatitis: A Major Risk Factor for HCC;274
13.3;3. Proteomic Identification of Biomarkers of Liver Cancer;275
13.4;4. Glycomic Methodologies for the Identification of Biomarkers of Liver Cancer;276
13.5;5. Fucosylation is Not Universally Increased in HCC Tissue as Compared to Adjacent or Control Tissue;280
13.6;6. Increased Branching is Observed in HCC Tissue;282
13.7;7. Effect of Glycosylation on Hepatocyte Growth;283
13.8;8. Conclusion;283
13.9;References;284
14;Chapter 8: Functional Impact of Tumor-Specific N-Linked Glycan Changes in Breast and Ovarian Cancers;296
14.1;1. Introduction;297
14.1.1;1.1. Introduction to the synthesis of glycan structures;297
14.1.2;1.2. History of research to identify glycan changes in cancer;298
14.1.3;1.3. Introduction to breast and ovarian cancer;298
14.2;2. N-Linked Glycans;300
14.2.1;2.1. GnT-V;302
14.2.2;2.2. GnT-III;304
14.2.3;2.3. GnT-IV;305
14.2.4;2.4. FUT8;306
14.2.5;2.5. High mannose;307
14.2.6;2.6. Terminal glycan structures;307
14.3;3. Concluding Remarks;311
14.4;Acknowledgments;311
14.5;References;311
15;Chapter 9: Glycosylation Alterations in Lung and Brain Cancer;320
15.1;1. Introduction;321
15.1.1;1.1. Altered glycosylation in cancer;321
15.1.2;1.2. Lung cancer;322
15.1.3;1.3. Brain cancer;323
15.2;2. N-Linked Glycans;324
15.3;3. O-Linked Glycans;326
15.4;4. Mucins;328
15.5;5. Sialic Acid;330
15.6;6. Fucosylation;332
15.7;7. Heparan Sulfate Proteoglycans and Their Modifying Enzymes;335
15.8;8. Clinical Significance;340
15.8.1;8.1. Biomarkers;341
15.8.1.1;8.1.1. HSPGs and their modifying enzymes;341
15.8.1.2;8.1.2. Mucins;342
15.8.1.3;8.1.3. Fucosylation;343
15.8.1.4;8.1.4. Glycosylation of serum proteins;343
15.8.2;8.2. Therapeutics;344
15.9;References;346
16;Chapter 10: Altered Glycosylation in Prostate Cancer;360
16.1;1. Introduction;361
16.2;2. Current Glycoprotein Biomarkers of Prostate Cancer;363
16.2.1;2.1. Properties of PSA;363
16.2.2;2.2. Glycosylation of PSA;364
16.2.3;2.3. Properties and glycosylation of prostatic acid phosphatase;369
16.3;3. N-Linked Glycosylation in Prostate Tissues;370
16.3.1;3.1. Background and historical studies;370
16.3.2;3.2. Glycoproteomic approaches;371
16.3.3;3.3. Cryptic N-glycans;372
16.3.4;3.4. Glycopathology-MALDI mass spectrometry tissue imaging of glycans;375
16.4;4. N-Linked Glycosylation in Prostate Cancer Proximal Biofluids and Exosomes;378
16.4.1;4.1. Seminal plasma and prostatic fluids;378
16.4.2;4.2. Serum and plasma;380
16.4.3;4.3. Exosomes;382
16.5;5. Glycosylation in Prostate Cancer Cell Lines;383
16.5.1;5.1. Representative examples;383
16.5.2;5.2. Metabolic labeling with azide sugars and glycoproteomics;385
16.6;6. O-Linked Glycosylation in Prostate Cancer;386
16.6.1;6.1. Mucins;386
16.7;7. Glycolipids in Prostate Cancer;387
16.7.1;7.1. Gangliosides and other glycosphingolipids;387
16.7.2;7.2. F77 antigen and prostate tumor glycolipid antigen;388
16.8;8. Summary;388
16.9;References;390
17;Index;398
18;Color Plate;409

Leseproben

Chapter Two Glycans and Cancer
Role of N-Glycans in Cancer Biomarker, Progression and Metastasis, and Therapeutics
Naoyuki Taniguchi1; Yasuhiko Kizuka    Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKEN, Wako, Saitama, Japan
1 Corresponding author: email address: [e-mail] Abstract
Glycosylation is catalyzed by various glycosyltransferase enzymes which are mostly located in the Golgi apparatus in cells. These enzymes glycosylate various complex carbohydrates such as glycoproteins, glycolipids, and proteoglycans. The enzyme activity of glycosyltransferases and their gene expression are altered in various pathophysiological situations including cancer. Furthermore, the activity of glycosyltransferases is controlled by various factors such as the levels of nucleotide sugars, acceptor substrates, nucleotide sugar transporters, chaperons, and endogenous lectin in cancer cells. The glycosylation results in various functional changes of glycoproteins including cell surface receptors and adhesion molecules such as E-cadherin and integrins. These changes confer the unique characteristic phenotypes associated with cancer cells. Therefore, glycans play key roles in cancer progression and treatment. This review focuses on glycan structures, their biosynthetic glycosyltransferases, and their genes in relation to their biological significance and involvement in cancer, especially cancer biomarkers, epithelial–mesenchymal transition, cancer progression and metastasis, and therapeutics. Major N-glycan branching structures which are directly related to cancer are ß1,6-GlcNAc branching, bisecting GlcNAc, and core fucose. These structures are enzymatic products of glycosyltransferases, GnT-V, GnT-III, and Fut8, respectively. The genes encoding these enzymes are designated as MGAT5 (Mgat5), MGAT3 (Mgat3), and FUT8 (Fut8) in humans (mice in parenthesis), respectively. GnT-V is highly associated with cancer metastasis, whereas GnT-III is associated with cancer suppression. Fut8 is involved in expression of cancer biomarker as well as in the treatment of cancer. In addition to these enzymes, GnT-IV and GnT-IX (GnT-Vb) will be also discussed in relation to cancer. Keywords Glycosyltransferases Cancer biomarker E-cadherin Integrins Epithelial–mesenchymal transition Cancer progression and metastasis GnT-III GnT-IV GnT-V GnT-Vb (GnT-IX) Fut8 1 Introduction
Glycans are present as free forms or conjugated forms in mammalian tissues and most are components of various glycoconjugates such as glycoproteins, glycolipids, and proteoglycans. In addition to those glycoconjugates, free glycans such as monosaccharides, oligosaccharides, and polysaccharides are also present in eukaryotic cells. Glycosylation is the most frequent and well-known posttranslational modification reaction and probably is much more frequent than phosphorylation. For instance, O-GlcNAcylation, which is cytosolic and nuclear glycosylation, is one of the most frequent modification reactions in various proteins including metabolic enzymes and transcription factors. Glycosylation is catalyzed by the enzymatic reaction of glycosyltransferases whose encoding genes are nearly equivalent to 1–2% of human genome. Over 200 glycosyltransferase genes have been identified to date, and some of them form a glycosyltransferase gene family. Donor substrates for glycosyltransferases are nucleotide sugars including UDP-Gal, UDP-GlcNAc, GDP-fucose, and CMP-NANA, and acceptor substrates are mostly glycoconjugates. Because glycans are so heterogeneous, these glycosyltransferases can produce different kinds of glycans with strict substrate specificity. Aberrant glycosylation occurs frequently in cancer, and these modifications are characteristics of cancer cells or cancer tissues (Hakomori, 1996, 2001, 2002; Taniguchi, Miyoshi, Gu, Honke, & Matsumoto, 2006; Taniguchi, Miyoshi, Ko, Ikeda, & Ihara, 1999). Moreover, glycosylation plays a pivotal role in cancer progression and metastasis, cell–cell contact, and epithelial–mesenchymal transition (EMT) in cancer cells (Chen et al., 2013; Kalluri & Weinberg, 2009; Li et al., 2014; Pinho et al., 2012; Tan et al., 2014; Terao et al., 2011; Xu et al., 2012). In recent years, EMT has become the important issue for understanding the development and metastasis of cancer (Kalluri & Weinberg, 2009), and in fact, changes in N-glycan structures are considered to be important for understanding the significance of EMT and the resultant change of adhesive properties of cancer cells (Chen et al., 2013; Li et al., 2014; Pinho et al., 2012; Tan et al., 2014; Terao et al., 2011; Xu et al., 2012). Most of the cancer biomarkers that are in use today are glycoproteins or glycolipids, and they are measured immunochemically using monoclonal antibodies (Packer et al., 2008). The epitope for these monoclonal antibodies against glycoproteins are mostly toward the protein moiety and not toward the glycan structures. Currently, however, it is difficult to detect the early stage of cancer by using these antibodies. Several attempts have been conducted to detect specific glycosylation changes in glycoproteins for the early diagnosis of cancer patients. So far, only one antibody has been approved by FDA for the early detection of a cancer biomarker (Srivastava, 2013). Application of glycan changes for therapeutics is one of the current strategies for cancer treatment. Deletion of a specific glycan or the modification of glycan chains with fucose or sialic acid enhances antibody-dependent cellular cytotoxity (ADCC) which is a key player in killing the cancer tissues (Satoh, Iida, & Shitara, 2006; Shields et al., 2002; Shinkawa et al., 2003). This review focuses on the biological significance of branched N-glycans and their implication in cancer biomarkers, progression and metastasis of cancer, and therapeutics. The major N-glycan branching enzymes discussed in this review, GnT-III, GnT-IV, GnT-V, and GnT-IX (Vb), and Fut8, and their product glycans, are shown in Fig. 1. Figure 1 Major glycosyltransferases that are involved in branching of N-glycan and O-mannose glycan 2 Metabolic Pathway of Branched N-Glycans and Their Corresponding Glycosyltransferases
It is well known that the N-glycosylation machinery begins with a common precursor containing a glycan consisting of 14 monosaccharide units (3 d-glucose, 9 d-mannose, and 2 N-acetyl-d-glucosamine residues) which is incorporated in the protein back bone in the rough endoplasmic reticulum (ER). They are processed in ER and Golgi apparatus by specific glycosidases and glycosyltransferases (Ohtsubo & Marth, 2006). Most of the branching structures are formed by various glycosyltransferases such as GnTs (N-acetylglucosaminyltransferases), Futs (fucosyltransferases), GalTs (galactosyltransferases), and STs (sialyltransferases) in the Golgi apparatus. Among them, GnT-I to GnT-VI act on a common core structure of Mana1–6 (Mana1–3) Manß1–4GlcNAcß1–4GlcNAcß1-Asn (Stanley, Schachter, & Taniguchi, 2009; Taniguchi, Gu, Takahashi, & Miyoshi, 2004) (Fig. 1). Glycosylation is regulated by various factors including the availability of nucleotide sugars as donor substrates, acceptor substrates, cofactors, nucleotide sugar transporters, endogenous lectins, chaperons, localization within the cell, etc. (Brockhausen, Narasimhan, & Schachter, 1988; Taniguchi, 2009). Therefore in relation to the role of glycans in cancer, the above regulation mechanism should be also kept in mind. Our group previously developed the method for the simultaneous analysis of nucleotide sugars by ion-paired high-performance liquid chromatography (HPLC). This method enabled us to carry out a quantitative analysis using 1 × 106 cells. By using this technique, we found marked changes in nucleotide sugars in beast and pancreatic cell lines (Nakajima et al., 2010). We also developed an isotopomer analysis method for evaluating the metabolic flow of glycans by using C6-labeled glucose and C2-labeled glucosamine followed by the mass topomer analysis (Nakajima et al., 2013). These metabolic analyses of mass isotopomers using LC-MS also provide us with useful information for understanding the glycan metabolism in cancer cells. 2.1 Fut8 (FUT8, Fut8)
2.1.1 Enzymatic properties and gene regulation a1,6-Fucose (core fucose) plays various roles in terms of cancer. a1,6-Fucosylation of N-glycans occurs ubiquitously in eukaryote except plant and fungi. This type of fucosylation is catalyzed by the a1,6-fucosyltransferase (Fut8) in mammalian tissues. Fut8 transfers a fucose moiety from...