Novel Methods and Pathways in Cancer Glycobiology Research

1st Edition, Volume 157 - February 2, 2023
Editors: Charles J Dimitroff, Karen Abbott
Language: English
Hardback ISBN:
9 7 8 - 0 - 3 2 3 - 9 9 1 7 7 - 3
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 9 1 7 8 - 0

Cancer glycobiology is a blazing hot area of cancer research with aberrant post-translational glycosylations on lipids and proteins considered critical for cancer development an… Read more

Novel Methods and Pathways in Cancer Glycobiology Research

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Cancer glycobiology is a blazing hot area of cancer research with aberrant post-translational glycosylations on lipids and proteins considered critical for cancer development and metastasis. The NIH/NCI Alliance of Glycobiologists for Cancer Research is a consortium of (10) tumor glycobiology laboratories funded to investigate how cancer-associated glycans (CAG) impact the development and metastasis of cancer. The hope of this momentous effort is to discover CAGs for use as novel biomarkers to detect early-stage cancer or its aggressive behavior or, alternatively, as novel molecular targets with the promise of a curative approach to cancer therapy. The mission of the ‘Alliance’ is to study structure and function of CAGs in cancer development and to provide clinically useful biomarkers for detecting cancer early or the potential of metastasis. This charge has stimulated extensive collaborations across US and International institutions to accelerate discovery of glycan-based biomarkers to the forefront of NCI's efforts to diagnose early-stage cancer and provide curative anti-cancer therapies.

The main goals of these research efforts are:
1. To identify and study how cancer-associated glycans functionally impact cancer growth and metastasis
2. To identify cancer-associated glycans that can serve as biomarkers for the detection or progression of cancer
3. To develop cancer-associated glycans as novel therapeutic targets for the treatment and cure of cancer

This volume consists of (9) chapters, one from each funded laboratory, that reviews new methods and mechanisms highlighting glycoconjugates and their roles as cancer biomarkers and/or anti-cancer therapeutic targets.

Cover image
Title page
Table of Contents
Copyright page
Contributors
Collaborative Spirit Drives the Field of Tumor Glycobiology: A Preface to Special Volume on Cancer Glycobiology
Chapter One: The clinical role of glycobiology on ovarian cancer progression
Abstract
1 Introduction
2 Functional significance of altered glycosylation and their roles in ovarian cancer
3 Mucins and mucin domain containing glycoproteins in ovarian cancer
4 The significance of glycolipids and lipid linked glycoproteins in ovarian cancer development and progression
5 Conclusions
Acknowledgments
References
Chapter Two: Mass spectrometry based biomarkers for early detection of HCC using a glycoproteomic approach
Abstract
1 Introduction
2 Glycomics of liver disease
3 MS-bases analyses of glycan and glycopeptide isomers associated with liver diseases
4 Glycopeptide structural configurations can serve as biomarkers for cancer detection
5 Future directions
Acknowledgements
References
Chapter Three: Beyond glyco-proteomics—Understanding the role of genetics in cancer biomarkers
Abstract
1 Introduction
2 Current cancer biomarkers
3 Aberrant glycosylation in cancer
4 Incorporation of genetics into biomarker development
5 Future directions and conclusions
References
Chapter Four: Measuring the multifaceted roles of mucin-domain glycoproteins in cancer
Abstract
Abbreviations
1 Introduction
2 Mucin-domain glycoproteins
3 Tools to study mucin-domain glycoproteins
4 Aberrant mucins in various cancer types
5 Roles of mucins in tumor growth and metastasis
6 Summary
Acknowledgments
References
Chapter Five: Role of tumor cell sialylation in pancreatic cancer progression
Abstract
1 Introduction
2 Hypersialylation of N-glycosylated proteins
3 Sialyl Lewis antigens
4 Sialylated forms of truncated O-glycans
5 Activation of Siglec receptors by tumor sialoglycans
6 Concluding remarks
Acknowledgments
References
Chapter six: The pleiotropic role of galectin-3 in melanoma progression: Unraveling the enigma
Abstract
1 Introduction
2 Gal-3 molecular structure
3 Regulation of Gal-3 expression
4 The subcellular and extracellular distribution of Gal-3
5 Extracellular and cell-intrinsic Gal-3-binding partners
6 Gal-3 involvement in cancer progression
7 Diagnostic and prognostic values of Gal-3 in melanoma
8 Gal-3 based therapeutic applications in melanoma
9 Conclusion
Conflicts of interest
Acknowledgment
References
Chapter Seven: Role of O-GlcNAcylation on cancer stem cells: Connecting nutrient sensing to cell plasticity
Abstract
1 Introduction
2 O-GlcNAcylation and cancer stem cells maintenance and function
3 OGT and O-GlcNAcylation in therapy resistance and tumor recurrence
4 Conclusion
Acknowledgments
References
Chapter Eight: The biology of E-selectin ligands in leukemogenesis
Abstract
1 Introduction
2 The glycosynthetic basis of E-selectin binding
3 Glycoconjugates that serve as E-selectin ligands
4 The biology of E-selectin in hematopoiesis
5 Conclusion
Acknowledgments
References
Chapter Nine: Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential
Abstract
1 Introduction
2 Aberrant HSPG expression in cancer and associated functional and clinical consequences
3 HSPG-modulated molecular pathways in cancer
4 Targeting heparan sulfate proteoglycan for therapeutic development
5 Conclusions
Conflict of interest
Authors’ contributions
Sources of Funding
References

Charles J Dimitroff

Over the last 26 years, Dr. Dimitroff has established himself as leader in field of glycobiology and is highly motivated to translate his glycobiological findings to help cure diseases and improve the health of humans. His research focuses on understanding how sugars or ‘glycans’ regulate immune and cancer cell functions with the goal of developing new approaches to boost the immune system to fight diseases and to treat cancer progression. These efforts have led to a laboratory that operates one of the preeminent translational glycobiology programs in the US. Dr. Dimitroff spent his initial years as an independent PI at Brigham and Women’s Hospital (BWH)/Harvard Medical School (HMS) transitioning from Instructor to Associate Professor of Dermatology in the Department of Dermatology. He was a Faculty Member in the Harvard Immunology Ph.D. Program and was the Associate Director for Laboratory Research in BWH Dermatology. In 2019, he then joined the Herbert Wertheim College of Medicine (HWCOM) at Florida International University (FIU) as the Executive Associate Dean for Research and Professor (with Tenure) of Translational Medicine. He now has concentrated his administrative duties focusing as the Founding Director of the Translational Glycobiology Institute at FIU (TGIF), wherein he oversees translational glycoscience research. The TGIF is a one-of-kind institute with translational glycoscience investigators seeking cures for diseases and providing research opportunities for trainees at all academic levels with a special focus on underrepresented minorities and women in science. Dr. Dimitroff’s current translational glycobiology research is subdivided into (2) Programs: a Solid Cancer Research Program and an Immune Research Program. In the Solid Cancer Research Program, his research explores the glycome of metastatic melanomas and ascertains how the glycome drives melanoma metastasis and whether these glycobiological features can be used as biomarkers to predict melanoma metastasis. In the Immune Research Program, his research investigates how human B cell glycans control B cell fate and function. These investigations have unveiled new molecular insights on the regulation of a humoral immune response and vaccinations, and the treatment of B cell malignancies.

Affiliations and expertise

Herbert Wertheim College of Medicine, Translational Glycobiology Institute, Department of Translational Medicine, Florida International University, FL, USA

Karen Abbott

Dr. Karen Abbott has been a leader in the field of glycoproteomics and biomarker discovery for over 14 years. Dr. Abbott received her PhD in Biochemistry at The University of Georgia in 2004. She was awarded an American Cancer Society Postdoctoral Fellowship in 2005 where she developed lectin capture methods for the analysis of glycoproteins from human tissues and plasma using mass spectrometry methods. She has been funded for ovarian cancer research by since 2010. She is currently funded by an Alliance of Glycobiologists NCI grant to understand how complex carbohydrates contribute to the development and progression of ovarian cancer. She is also currently funded by the NCI Innovative Molecular Analysis Technologies grant that supports the development of novel and transformative technologies to develop new therapeutics and diagnostics for cancer. Dr. Abbott joined the Herbert Wertheim College of Medicine (HWCOM) at Florida International University in 2020 as Associate Director for the Translational Glycobiology Institute. Her research is currently focused in three main areas: translational therapeutic development for ovarian cancer, studies on the role of Notch glycosylation in ovarian cancer progression, and technology development for the study of glycosylphosphatidylinositol anchored proteins.

Affiliations and expertise

Associate Professor, Department of Translational Medicine, Herbert Wertheim College of Medicine (HWCOM), Florida International University (FIU), and Assistant Director, Translational Glycobiology Institute at FIU (TGIF), a center focused on collaborative translational research that fosters an environment that supports mentoring of the next generation of scientists and promotes research excellence.