Journal
BRITISH JOURNAL OF CANCER
Volume 111, Issue 3, Pages 559-567Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2014.332
Keywords
angiogenesis; carbohydrate metabolism; endothelial cell; extracellular matrix; glycobiology; hyaluronate; oligosaccharide; tumour interstitial fluid
Categories
Funding
- Deutsche Forschungsgemeinschaft Schwerpunkt Program SPP1190 (Tumour-vessel interface)
- Glykobiologie/Glykomik of the Baden-Wurttemberg Stiftung
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Background: Association studies have implicated the glycosaminoglycan hyaluronan (hyaluronic acid, HA) and its degrading enzymes the hyaluronidases in tumour progression and metastasis. Oligosaccharides of degraded HA have been ascribed a number of biological functions that are not exerted by high-molecular-weight HA (HMW-HA). However, whether these small HA oligosaccharides (sHA) have a role in tumour progression currently remains uncertain due to an inability to analyse their concentration in tumours. Methods: We report a novel method to determine the concentration of sHA ranging from 6 to 25 disaccharides in tumour interstitial fluid (TIF). Levels of sHA were measured in TIF from experimental rat tumours and human colorectal tumours. Results: While the majority of HA in TIF is HMW-HA, concentrations of sHA up to 6 mu g ml(-1) were detected in a subset of tumours, but not in interstitial fluid from healthy tissues. In a cohort of 72 colorectal cancer patients we found that increased sHA concentrations in TIF are associated with lymphatic vessel invasion by tumour cells and the formation of lymph node metastasis. Conclusions: These data document for the first time the pathophysiological concentration of sHA in tumours, and provide evidence of a role for sHA in tumour progression.
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