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Emerging Roles for Hyaluronidase in Cancer Metastasis and Therapy
Open accessAbstract
Hyaluronidases are a family of five human enzymes that have been differentially implicated in the progression of many solid tumor types, both clinically and in functional studies. Advances in the past 5 years have clarified many apparent contradictions: (1) by demonstrating that specific hyaluronidases have alternative substrates to hyaluronan (HA) or do not exhibit any enzymatic activity, (2) that high-molecular weight HA polymers elicit signaling effects that are opposite those of the hyaluronidase-digested HA oligomers, and (3) that it is actually the combined overexpression of HA synthesizing enzymes with hyaluronidases that confers tumorigenic potential. This review examines the literature supporting these conclusions and discusses novel mechanisms by which hyaluronidases impact invasive tumor cell processes. In addition, a detailed structural and functional comparison of the hyaluronidases is presented with insights into substrate selectivity and potential for therapeutic targeting. Finally, technological advances in targeting hyaluronidase for tumor imaging and cancer therapy are summarized.
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“In addition, hyaluronidase, γ-Glutamyltranspeptidase, prostate-specific antigen, Trysin, β-galactosidase, Azoreductase, etc. are also used in enzyme-stimulated response smart nano-delivery systems.157–162”
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Metadata
- Authors
- McAtee, C. O., Barycki, J. J., & Simpson, M. A.
- Affiliations
- University of Nebraska–Lincoln (US)
- Corresponding author
- Melanie A. Simpson
- Venue
- Advances in Cancer Research
- Publisher
- Elsevier
- Published
- 2014
- Volume
- 123
- Pages
- 1-34
- ISSN
- 0065-230X (ISSN-L)
- PMC
- PMC4445717
- OpenAlex
- W2394990651
- Cited by
- 204
- References
- 127
- Citations by year
- 2026: 3 · 2025: 17 · 2024: 14 · 2023: 24 · 2022: 19 · 2021: 20 · 2020: 25 · 2019: 28 · 2018: 14 · 2017: 15 · 2016: 12 · 2015: 12 · 2014: 1
- FWCI
- 18.61
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Advances in cancer research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- Funders
- National Institutes of Health (8p20gm103489-10)
- National Cancer Institute (R01CA165574)
- National Institute of General Medical Sciences (P20-GM103489)
- National Center for Research Resources (P20RR018759)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- hyaluronidase, hyaluronic acid, metastasis, tumor invasion, hyaluronan oligosaccharides, hyaluronan synthase, substrate specificity, enzyme structure, hyaluronidase inhibitors, tumor imaging, cancer therapy
- MeSH terms
- Animals, Cell Movement, Fibroblasts, Humans, Hyaluronic Acid, Hyaluronoglucosaminidase, Molecular Conformation, Molecular Weight, Neoplasm Metastasis, Neoplasms, Polymers, Prognosis, Alternative Splicing, Disease Progression, Mole Rats, Rats
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