Elevate Level of Glycosaminoglycans and Altered Sulfation Pattern of Chondroitin Sulfate Are Associated with Differentiation Status and Histological Type of Human Primary Hepatic Carcinoma

Abstract

Objectives: The characteristics of glycosaminoglycans (GAGs) in many carcinomas have been reported to be different from those in normal tissues, which can be used as prognostic indices in some cancers. However, the difference in GAG characteristics among various differentiation status or histological types of the same cancer has not been described. The aim of this study was to investigate the relationship between GAG characteristics and human primary hepatic carcinomas of divers differentiation status or histological type. Methods: GAGs from intrahepatic cholangiocarcinomas and differently differentiated hepatocellular carcinomas were extracted, purified and enzymatically digested. Their content, relative molecular size distribution and disaccharide composition were analyzed and compared using electrophoresis and high-performance liquid chromatography. Results: A progressive increase in the content of chondroitin sulfate, low molecular size GAGs, and nonsulfated and disulfated chondroitin sulfate disaccharide units, together with a gradual decrease in heparan sulfate, have been found as the differentiation status of hepatocellular carcinoma became poorer. A significant increase in hyaluronic acid, which only slightly increased in hepatocellular carcinoma, was found in intrahepatic cholangiocarcinomas. Conclusion: The alterations in GAG characteristics in primary hepatic carcinoma were associated with both the differentiation status and the histological type of the tumor.

Involvement of Highly Sulfated Chondroitin Sulfate in the Metastasis of the Lewis Lung Carcinoma Cells

“…Furthermore, our results showed that CS-E decasaccharides were minimal oligosaccharides with substantial inhibitory activity against the metastasis of LM66-H11 cells, which is consistent with the notion that CS-E-derived decasaccharides were the minimal size required for the binding of the antibody GD3G7 (29). A few studies have addressed that CS-PGs play a major role in cancer cell behavior (57) and that alterations in their expression and function during transformation facilitate tumor progression (57). However, the expression of specific CS/DS structures has not been correlated to tumor aggressiveness.…”

Overexpression of Hyaluronan-binding Protein 1 (HABP1/p32/gC1qR) in HepG2 Cells Leads to Increased Hyaluronan Synthesis and Cell Proliferation by Up-regulation of Cyclin D1 in AKT-dependent Pathway

“…Also, HA and other glycosaminoglycans (like chondroitin sulfate) are reported to be elevated in hepatic carcinomas (25). Additionally, HA is reported to have antioxidant properties and is known to act as a scavenger of chemical reactive oxygen intermediates in the extracellular space (26).…”

Endogenous Heparinoids Detected by anti-Xa Activity are Present in Blood during Acute Variceal Bleeding in Cirrhosis. A Prospective Study

“…Patients with HCC have circulating endogenous GAGs [25], and this is most likely re ected by the detected raised anti-Xa levels. In HCC, there are quantitative and qualitative abnormalities of GAGs in the cancer tissue compared to normal liver [26]. A progressive increase in the content of chondroitin sulfate, low molecular size GAGs, and non-sulfated and di-sulfated chondroitin sulfate disaccharide units, together with a gradual decrease in heparan sulfate, have been found as the di erentiation status of HCC becomes worse [26].…”