Expression of glycosaminoglycans in cirrhotic liver and hepatocellular carcinoma—a pilot study including etiology

Abstract

Chronic liver diseases have both high incidence and mortality rates; therefore, a deeper understanding of the underlying molecular mechanisms is essential. We have determined the content and sulfation pattern of chondroitin sulfate (CS) and heparan sulfate (HS) in human hepatocellular carcinoma and cirrhotic liver tissues, considering the etiology of the diseases. A variety of pathological conditions such as alcoholic liver disease, hepatitis B and C virus infections, and primary sclerosing cholangitis were studied. Major differences were observed in the total abundance and sulfation pattern of CS and HS chains. For example, the 6-O-sulfation of CS is fundamentally different regarding etiologies of cirrhosis, and a 2–threefold increase in HS N-sulfation/O-sulfation ratio was observed in hepatocellular carcinoma compared to cirrhotic tissues. Graphical abstract

Tumor decellularization reveals proteomic and mechanical characteristics of the extracellular matrix of primary liver cancer

“…S2). This suggests maintenance of tumor-specific sGAGs, particularly considering that PLC is related to changes in composition of sGAGs [28,29]. In summary, decellularization of liver cancer biopsies resulted in the successful production of acellular scaffolds, which preserve relevant components of the ECM.…”

Compositional Analysis of Glycosaminoglycans in Different Lung Cancer Types—A Pilot Study

“…Our results also revealed several significant changes in CS in relation to lung cancer. An increase in CS content has been observed in various tumor types, e.g., liver [ 20 ], prostate [ 19 ] highlighting the importance of CS in tumor formation. In our experiments, CS expression increased in tumor samples, implying the increased activity of enzymes involved in their formation.…”

“…Sulfation along the chain is carried out by sulfotransferase enzymes [ 17 ]. Changes in the total quantity of GAG chains and in their sulfation patterns have been previously identified between healthy and tumor tissue [ 18 , 19 , 20 ]. Chondroitin sulfates (CS) and heparan sulfates (HS) are among the most important and most widely studied GAGs.…”

Inter- and intratumoral proteomics and glycosaminoglycan characterization of ALK rearranged lung adenocarcinoma tissues: a pilot study

“…First, CS digestion was performed by using 5 × 2 μL of digestion solution (2 mU/μL chondroitinase-ABC enzyme in a solution of 20 mM Tris (pH 7.6) + 2.5 mM ammonium acetate + 10% glycerol) on each region. Samples were incubated in a humidified box at 37 °C for 60 min during each cycle, and the last drop was left on the tissue surface for a total of 24 h from the start of digestion 56 , 64 . The liquid drops were pipetted off and the remaining disaccharides were extracted by 5 × 2 μL of 1% NH 3 solution, then the drops were collected and the solvents were evaporated.…”

“…The concentration of the enzyme solution applied was 0.5 mU/μL for heparin lyase I and 0.1 mU/μL for heparin lyase II and III, in a solution of 20 mM Tris (pH 7.6) + 2.5 mM Ca(OH) 2 + 10% glycerol. The digestion was performed for 48 h in a humidified box at 37 °C with 5 × 2 μL digestion solution, which were added after 0, 1, 2, 19 and 26 h from the start of the digestion 56 , 64 . Extraction was carried out the same way as for CS disaccharides.…”