Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid correlates with lymphatic invasion and lymph node metastasis.
Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid correlates with lymphatic invasion and lymph node metastasis.
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DOI：
10.1038/bjc.2014.332
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发表时间：
2014-07-29
影响因子：
8.8
通讯作者：
Sleeman, J. P.
中科院分区：
文献类型：
--
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.
关键词：
相关研究表明，糖胺聚糖透明质酸(HA)及其降解酶透明质酸酶与肿瘤的进展和转移有关。降解的HA寡糖被认为具有许多高分子量HA(HMW-HA)所不具备的生物学功能。然而，这些小的HA寡糖(SHA)是否在肿瘤进展中起作用目前仍不确定，因为无法分析它们在肿瘤中的浓度。我们报道了一种新的方法来测定肿瘤间质液(TIF)中6到25个双糖的浓度。从实验大鼠肿瘤和人类结直肠癌的TIF中检测SHA的水平。在部分肿瘤组织中检测到高达6 μg ml−-1的HA，而在正常组织的间质液中检测不到。在一组72例结直肠癌患者中，我们发现TIF中HA浓度的升高与肿瘤细胞对淋巴管的侵袭和淋巴结转移的形成有关。这些数据首次证明了SHA在肿瘤中的病理生理浓度，并为SHA在肿瘤进展中的作用提供了证据。
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. 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. While the majority of HA in TIF is HMW-HA, concentrations of sHA up to 6 μg 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. 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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影响因子：
11.2
作者：
Benitez A;Yates TJ;Lopez LE;Cerwinka WH;Bakkar A;Lokeshwar VB
通讯作者：
Lokeshwar VB
影响因子：
--
作者：
Dang S;Peng Y;Ye L;Wang Y;Qian Z;Chen Y;Wang X;Lin Y;Zhang X;Sun X;Wu Q;Cheng Y;Nie H;Jin M;Xu H
通讯作者：
Xu H
影响因子：
33.6
作者：
Jiang D;Liang J;Noble PW
通讯作者：
Noble PW
影响因子：
6
作者：
Bharadwaj, Alamelu G.;Kovar, Joy L.;Simpson, Melanie A.
通讯作者：
Simpson, Melanie A.
影响因子：
2.9
作者：
David-Raoudi, Maha;Tranchepain, Frederic;Pujol, Jean-Pierre
通讯作者：
Pujol, Jean-Pierre