The asialoglycoprotein receptor in human hepatocellular carcinomas: its expression on proliferating cells

The expression of the asialoglycoprotein receptor (ASGP-R) on human hepatocellular carcinoma (HCC) cells might be exploited to reduce the extrahepatic toxicity of DNA synthesis inhibitors by their conjugation with galactosyl-terminating peptides. In the present study we first assessed the frequency of ASGP-R expression in 60 HCCs. Secondly, we investigated whether the receptor was maintained on the plasma membranes of DNA synthesizing cancer cells. Needle biopsies of HCC were evaluated. Diagnosis and grading of HCC were performed on routine haematoxylin and eosin-stained sections according to Edmondson and Steiner (1953). Thirty-five tumours were grade I and II and were classified as well differentiated, while 25 tumours were grade III and IV and were classified as poorly differentiated. Sections from formalin-fixed, paraffin-embedded samples were incubated, after antigen retrieval, with an anti-ASGP-R monoclonal antibody revealed by secondary biotinylated antibody and streptavidin–biotin–peroxidase–diaminobenzidine reaction. A clear immunolabelling of plasma membranes of HCC cells was observed in 28 out of 35 (80%) well differentiated (grade I and II) and in five out of 25 (20%) poorly differentiated (grade III and IV) HCCs. The presence of the ASGP-R on the surface of DNA synthesizing cancer cells was also investigated after in vitro bromodeoxyuridine (BrdU) labelling of HCC samples by immunohistochemical visualization of both the ASGP-R and incorporated BrdU on the same section. The results obtained clearly demonstrated that DNA synthesizing cancer cells expressed the ASGP-R on their surface. The presence of ASGP-R on cell plasma membrane in the majority of differentiated HCCs and its maintenance on proliferating cells encourages studies in order to restrict the action of the inhibitors of DNA synthesis of HCC cells by their conjugation with galactosyl-terminating carriers internalized through this receptor. © 1999 Cancer Research Campaig

Relationship between interphasic nucleolar organizer regions and growth rate in two neuroblastoma cell lines.

The relationship between the quantity of silver-stained interphasic nucleolar organizer regions (NORs) and nuclear synthetic activity, caryotype, and growth rate was studied in two established neuroblastoma cell lines (CHP 212 and HTB 10). Statistical analysis of silver-stained NORs revealed four times as many in CHP 212 cells compared with HTB 10 cells. No difference was observed in the ribosomal RNA synthesis between the two cell lines. The caryotype index was 1.2 for CHP 212 and 1.0 for HTB 10 cells. The number of chromosomes carrying NORs and the quantity of ribosomal genes was found to be the same for the two cell lines. Doubling time of CHP 212 cells was 20 hours compared with 54 hours for HTB 10 cells. In CHP 212 cells bindering of cell duplication by serum deprivation induced a progressive lowering (calculated at 48, 72, and 96 hours) of the quantity of silver-stained interphasic NORs. Recovery of duplication by new serum addition induced, after 24 hours, an increase of the quantity of silver-stained interphasic NORs up to control levels. In the light of available data, these results indicate that the quantity of interphasic NORs is strictly correlated only to the growth rate of the cell