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肿瘤间质液中小透明质酸寡糖的积累与淋巴管浸润和淋巴结转移相关。

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

机构信息

1] Medical Faculty Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 13-17, 68167 Mannheim, Germany [2] Karlsruhe Institute for Technology (KIT), Campus Nord, Institut für Toxikologie und Genetik, Postfach 3640, 76021 Karlsruhe, Germany.

Institut und Gemeinschaftspraxis für Pathologie an den St Vincentiuskliniken Karlsruhe, Südendstrasse 37, 76137 Karlsruhe, Germany.

出版信息

Br J Cancer. 2014 Jul 29;111(3):559-67. doi: 10.1038/bjc.2014.332. Epub 2014 Jun 17.

DOI:10.1038/bjc.2014.332
PMID:24937668
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4119989/
Abstract

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 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.

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.

摘要

背景

关联研究表明糖胺聚糖透明质酸（透明质酸，HA）及其降解酶透明质酸酶在肿瘤的进展和转移中起作用。降解后的 HA 的低聚糖具有多种生物学功能，而高分子量 HA（HMW-HA）则不具有这些功能。然而，由于无法分析肿瘤中 sHA 的浓度，这些小分子 HA 寡糖（sHA）是否在肿瘤进展中起作用目前仍不确定。

方法

我们报告了一种新的方法来测定肿瘤间质液（TIF）中 sHA 的浓度，范围为 6 至 25 个二糖。在实验性大鼠肿瘤和人结直肠肿瘤的 TIF 中测量了 sHA 的水平。

结果

虽然 TIF 中的大多数 HA 都是 HMW-HA，但在一部分肿瘤中检测到高达 6μg/ml 的 sHA 浓度，但在健康组织的间质液中则没有。在 72 名结直肠癌患者的队列中，我们发现 TIF 中 sHA 浓度的增加与肿瘤细胞的淋巴管浸润和淋巴结转移的形成有关。

结论

这些数据首次记录了肿瘤中 sHA 的病理生理浓度，并为 sHA 在肿瘤进展中的作用提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/d14e8a5c6588/bjc2014332f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/5745f77ef9fc/bjc2014332f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/c2c6aba40715/bjc2014332f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/28730145ff8a/bjc2014332f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/f6fe40ac2905/bjc2014332f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/754c49747311/bjc2014332f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/d14e8a5c6588/bjc2014332f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/5745f77ef9fc/bjc2014332f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/c2c6aba40715/bjc2014332f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/28730145ff8a/bjc2014332f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/f6fe40ac2905/bjc2014332f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/754c49747311/bjc2014332f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a96/4119989/d14e8a5c6588/bjc2014332f6.jpg

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