Tumour Angiogenesis and Metastasis: The Regulatory Role of Hyaluronan and Its Degradation Products
Hyaluronan (HA, previously termed hyaluronic acid) is a high molecular weight glycosaminoglycan, a linear polysaccharide made up of a repeating disaccharide unit [D-glucuronic acid (l-β-3) N-acetyl-D-glucosamine] linked by l-β-4 glycosidic bonds. It is present in the extracellular matrix of most animal tissues and this ubiquitous distribution, its capacity to bind large amounts of water, and its simple structure led to the general belief that it was essentially a structural, or space filling, molecule. However, in the last ten years HA has been shown to profoundly influence cell behaviour. Transient increases in tissue HA levels coincide with rapid cell proliferation and migration, during embryonic development and the regeneration and remodelling of adult tissues. Localized accumulation has been reported in association with tissue damage, organ rejection and many inflammatory diseases, notably psoriasis and scleroderma, and it is a major component of many tumours(Laurent and Fraser, 1992; Knudson et al., 1989). The temporal and spatial distribution of HA during embryogenesis, and tissue remodelling, suggests that the sythesis and degradation of HA plays an important regulatory role in these processes, and certain pathological conditions such as tumour growth.
KeywordsVascular Endothelial Growth Factor Hyaluronic Acid Angiogenic Activity Hyaluronidase Activity Repeat Disaccharide Unit
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