Differential Expression of β-Galactoside α2,6 Sialyltransferase and Sialoglycans in Normal and Cirrhotic Liver and Hepatocellular Carcinoma

Abstract

SUMMARY:Sialyltransferases sialylate plasma glycoproteins in hepatocytes and may (as hepatic key enzymes) constitute markers for liver diseases. We examined expression of the prevalent ␣2,6 sialyltransferase (ST6Gal I) and sialoglycans in normal liver, cirrhotic liver, and hepatocellular carcinoma (HCC) using a new ST6Gal I-specific mAb and recombinant fusion proteins of CD22 and sialoadhesin recognizing ␣2,6-or ␣2,3-sialylated glycans in immunohistology and flow cytometry. In normal and cirrhotic liver, ST6Gal I and sialoglycans were localized in the Golgi region of hepatocytes surrounding the bile canaliculi and along the bile canaliculi, respectively. Sialoglycans were additionally recognized in Kupffer cells, bile ducts, endothelial cells, and oval cells. Well-differentiated and moderately differentiated HCC showed Golgi and diffuse cytoplasmic staining of ST6Gal I and sialoglycans, whereas the cytoplasmic staining for ST6Gal I and sialoglycans was decreased or even absent in poorly differentiated HCC. Detection of sialoglycans by the recombinant fusion proteins in Western blots of cell lysates derived from cell lines revealed two major double bands of sialoglycoproteins at 65 and 120 kDa for hepatocytes, three major bands at 54, 49, and 44 kDa for colonic epithelial cells, and one band at 60 kDa for endothelial cells. Our results describe the expression patterns of ST6Gal I and sialoglycans in various liver tissues and demonstrate an altered expression of these structures between benign and malignant hepatocellular lesions. (Lab Invest 2002, 82:1515-1524.

α-Methylacyl-CoA Racemase (AMACR/P504S) Can Distinguish Hepatocellular Carcinoma and Dysplastic Hepatocytes From Benign Nondysplastic Hepatocytes

“…not been successful in differentiating HCC from benign liver tissue. [15][16][17][18][19] In the present study, we found that the pattern of immunostaining for AMACR distinguished benign nondysplastic hepatocytes from dysplastic or malignant hepatocytes. Dysplastic and malignant hepatocytes demonstrated a coarsely granular staining pattern with either a basal or diffuse distribution.…”

Alteration of protein glycosylation in liver diseases

“…Some evidence can also be found that the expression of ST6GalI is up-regulated in human HCC patients and in a transgenic mouse model of HCC [47][48][49]. We already mentioned this enzyme in ALD where it was down-regulated.…”

Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3as a novel lung cancer-related gene

“…Briefly, the cells grown on coverslips were fixed in −20°C acetone for 10 minutes and then incubated with the rabbit anti-ERGIC3 polyclonal antibody (Abcam), and anti-MUC1 mouse monoclonal antibody (mAb) A76-A/C7 (Glycotope, Berlin, Germany), anti-ST mAb [15], anti-calreticulin mAb (Abcam), and anti-58K Golgi protein mAb (Abcam) at 4°C overnight. Following the washes, the cells were incubated with FITC-coupled anti-rabbit antibody (BD sciences, Franklin Lakes, NJ, USA) or with Cy3-coupled anti-mouse antibody (Millipore, Billerica, MA, USA) for 1 hour.…”