Hypoxia-Induced Alterations in Hyaluronan and Hyaluronidase
Abstract
Hyaluronan (HA), a large negatively-charged polysaccharide, is a major component of vessel basal membrane. HA is expressed by a variety of cells, including tumor and endothelial cells. We hypothesized that HA could be up-regulated by hypoxia to enhance vessel formation. To determine the effect of hypoxia on the production of HA, tumor cells were treated with either media alone (control) or a hypoxia inducer (CoCl or NaN3) for 24 h. The level of HA in the media was then measured by ELISA. The results showed that both CoCl and NaN3 induced the production of HA. Since the low molecular weight form of HA (SMW) possesses pro-angiogenic properties, we investigated whether hypoxia-induced HA can be processed into SMW. Under hypoxic conditions, the activity of hyaluronidase, the enzyme responsible for degrading HA, was measured by an ELISA-like assay. The activity of hyaluronidase was shown to be up-regulated by hypoxia and, further, could carry out the function of processing HA into SMW. In addition, the hypoxic areas of tumor tissues were stained strongly with biotinylated HA-binding proteins, indicating that the level of HA was high compared to the oxic areas. This study demonstrates that hypoxia can stimulate the production of HA and the activity of hyaluronidase, which may promote angiogenesis as a compensation mechanism for hypoxia.
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LMW-HA production likely occurs in cells cultured in low oxygen through enhanced activity of the HA-degrading enzyme hyaluronidase.
“Gao et al. have demonstrated that LMW-HA production likely occurs in cells cultured in low oxygen through enhanced activity of the HA-degrading enzyme hyaluronidase (50).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [50]
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- Authors
- Gao, F., Okunieff, P., Han, Z., Ding, I., Wang, L., Liu, W., Zhang, J., Yang, S., Chen, J., Underhill, C. B., Kim, S., & Zhang, L.
- Affiliations
- University of Rochester Medicine (US)
- Venue
- Advances in Experimental Medicine and Biology
- Publisher
- Springer US
- Published
- 2005
- Volume
- 566
- Pages
- 249-256
- ISSN
- 0065-2598 (ISSN-L)
- OpenAlex
- W1776594831
- Cited by
- 49
- References
- 29
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 5 · 2015: 2 · 2014: 4 · 2013: 4 · 2012: 1
- FWCI
- 4.68
- Type
- book chapter
- Language
- en
- Open access
- closed
- Licence
- Locations
- Advances in experimental medicine and biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ca071545-05)
- National Cancer Institute (CA71545)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- hyaluronic acid, hyaluronidase, hypoxia, tumor angiogenesis, low molecular weight hyaluronic acid, hyaluronan degradation, cobalt chloride, sodium nitrite, tumor hypoxia, hyaluronan-binding protein, extracellular matrix
- MeSH terms
- Acetylglucosaminidase, Animals, Hypoxia, Antigens, Neoplasm, beta-N-Acetylhexosaminidases, Breast Neoplasms, Female, Fibrosarcoma, Humans, Hyaluronic Acid, Hyaluronoglucosaminidase, Mice, Inbred C3H, Molecular Weight, Neoplasm Proteins, Neoplasms, Neovascularization, Pathologic, Cell Line, Tumor, Mice, Histone Acetyltransferases
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