Heparan sulfate proteoglycans undergo differential expression alterations in right sided colorectal cancer, depending on their metastatic character.
Heparan sulfate proteoglycans undergo differential expression alterations in right sided colorectal cancer, depending on their metastatic character.
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DOI：
10.1186/s12885-015-1724-9
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发表时间：
2015-10-20
期刊：
影响因子：
3.8
通讯作者：
Quirós LM
中科院分区：
文献类型：
--
作者：
Fernández-Vega I;García-Suárez O;García B;Crespo A;Astudillo A;Quirós LM
硫酸乙酰肝素蛋白聚糖（HSPG）是参与癌细胞的生长、侵袭和转移特性的复杂分子。本研究分析了这些分子在转移性和非转移性右侧结直肠癌（CRC）中表达模式的改变。研究了20个右侧CRC。使用转录组学方法，采用qPCR分析参与硫酸乙酰肝素（HS）链生物合成的酶以及蛋白聚糖核心蛋白的表达。由于这些蛋白聚糖也可以携带硫酸软骨素（CS）链，我们包括这些糖胺聚糖的生物合成中涉及的基因的研究。免疫组织化学技术还用于分析显示显着表达差异的潜在感兴趣的特定基因的组织表达。蛋白聚糖核心蛋白的变化根据其位置而不同;位于细胞内或细胞外基质中的蛋白聚糖核心蛋白显示出非常相似的改变模式，而位于细胞表面的蛋白聚糖核心蛋白则根据肿瘤的性质而变化很大：磷脂酰肌醇蛋白聚糖1、3、6和β聚糖在非转移性肿瘤中受到影响，而在转移性肿瘤中，仅磷脂酰肌醇蛋白聚糖-1和多配体聚糖-1被修饰，后者显示RNA和蛋白质水平的相反改变，表明这些肿瘤中的转录后调节。此外，在非转移性肿瘤中，糖胺聚糖链的聚合被修饰，特别是影响四糖接头的合成以及CS链的起始和延长，HS链受影响较小。关于负责HS链修饰的酶，仅在非转移性肿瘤中发现改变，影响N-硫酸化和亚型HS 6ST 1、HS 3ST 3B和HS 3ST 5。相反，CS链的合成表明两种类型肿瘤中C4和C2的差向异构化和硫酸化的变化。右侧CRC显示HSPG表达的改变，包括细胞表面核心蛋白、许多糖基转移酶和根据肿瘤的转移性质修饰HS链的一些酶的表达，导致非转移性CRC受到更多影响。然而，基质蛋白多糖和酶参与CS精细结构的合成广泛修改独立的淋巴结转移的存在。本文的在线版本（doi：10.1186/s12885-015-1724-9）包含补充材料，可供授权用户使用。
Heparan sulfate proteoglycans (HSPGs) are complex molecules involved in the growth, invasion and metastatic properties of cancerous cells. This study analyses the alterations in the expression patterns of these molecules in right sided colorectal cancer (CRC), both metastatic and non-metastatic. Twenty right sided CRCs were studied. A transcriptomic approach was used, employing qPCR to analyze both the expression of the enzymes involved in heparan sulfate (HS) chains biosynthesis, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate (CS) chains, we include the study of the genes involved in the biosynthesis of these glycosaminoglycans. Immunohistochemical techniques were also used to analyze tissue expression of particular genes showing significant expression differences, of potential interest. Changes in proteoglycan core proteins differ depending on their location; those located intracellularly or in the extracellular matrix show very similar alteration patterns, while those located on the cell surface vary greatly depending on the nature of the tumor: glypicans 1, 3, 6 and betaglycan are affected in the non-metastatic tumors, whereas in the metastatic, only glypican-1 and syndecan-1 are modified, the latter showing opposing alterations in levels of RNA and of protein, suggesting post-transcriptional regulation in these tumors. Furthermore, in non-metastatic tumors, polymerization of glycosaminoglycan chains is modified, particularly affecting the synthesis of the tetrasaccharide linker and the initiation and elongation of CS chains, HS chains being less affected. Regarding the enzymes responsible for the modificaton of the HS chains, alterations were only found in non-metastatic tumors, affecting N-sulfation and the isoforms HS6ST1, HS3ST3B and HS3ST5. In contrast, synthesis of the CS chains suggests changes in epimerization and sulfation of the C4 and C2 in both types of tumor. Right sided CRCs show alterations in the expression of HSPGs, including the expression of the cell surface core proteins, many glycosiltransferases and some enzymes that modify the HS chains depending on the metastatic nature of the tumor, resulting more affected in non-metastatic ones. However, matrix proteoglycans and enzymes involved in CS fine structure synthesis are extensively modified independetly of the presence of lymph node metastasis. The online version of this article (doi:10.1186/s12885-015-1724-9) contains supplementary material, which is available to authorized users.