Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid correlates with lymphatic invasion and lymph node metastasis

作者：Schmaus A; Klusmeier S; Rothley M; Dimmler A; Sipos B; Faller G; Thiele W; Allgayer H; Hohenberger P; Post S; Sleeman J P^*

来源：British Journal of Cancer, 2014, 111(3): 559-567.

DOI：10.1038/bjc.2014.332

• angiogenesis
• carbohydrate metabolism
• endothelial cell
• extracellular matrix
• glycobiology
• hyaluronate
• oligosaccharide
• tumour interstitial fluid

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2014-7-29