Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Oct;81(3):404–408. doi: 10.1038/sj.bjc.6690708

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

D Trerè 1,2, L Fiume 2, L Badiali De Giorgi 1, G Di Stefano 2, M Migaldi 3, M Derenzini 1,2
PMCID: PMC2362929  PMID: 10507763

Abstract

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 Campaign

Keywords: immunocytochemistry, drug targeting, bromodeoxyuridine, S phase

Full Text

The Full Text of this article is available as a PDF (286.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bruix J. Treatment of hepatocellular carcinoma. Hepatology. 1997 Feb;25(2):259–262. doi: 10.1053/jhep.1997.v25.ajhep0250259. [DOI] [PubMed] [Google Scholar]
  2. Di Stefano G., Busi C., Derenzini M., Trerè D., Fiume L. Conjugation of 5-fluoro-2'-deoxyuridine with lactosaminated poly-l-lysine to reduce extrahepatic toxicity in the treatment of hepatocarcinomas. Ital J Gastroenterol Hepatol. 1998 Apr;30(2):173–177. [PubMed] [Google Scholar]
  3. EDMONDSON H. A., STEINER P. E. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954 May;7(3):462–503. doi: 10.1002/1097-0142(195405)7:3<462::aid-cncr2820070308>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  4. Fiume L., Di Stefano G., Busi C., Mattioli A., Bonino F., Torrani-Cerenzia M., Verme G., Rapicetta M., Bertini M., Gervasi G. B. Liver targeting of antiviral nucleoside analogues through the asialoglycoprotein receptor. J Viral Hepat. 1997;4(6):363–370. doi: 10.1046/j.1365-2893.1997.00067.x. [DOI] [PubMed] [Google Scholar]
  5. Fiume L., Mattioli A., Balboni P. G., Tognon M., Barbanti-Brodano G., de Vries J., Wieland T. Enhanced inhibition of virus DNA synthesis in hepatocytes by trifluorothymidine coupled to asialofetuin. FEBS Lett. 1979 Jul 1;103(1):47–51. doi: 10.1016/0014-5793(79)81247-8. [DOI] [PubMed] [Google Scholar]
  6. Geffen I., Spiess M. Asialoglycoprotein receptor. Int Rev Cytol. 1992;137B:181–219. doi: 10.1016/s0074-7696(08)62605-4. [DOI] [PubMed] [Google Scholar]
  7. Hyodo I., Mizuno M., Yamada G., Tsuji T. Distribution of asialoglycoprotein receptor in human hepatocellular carcinoma. Liver. 1993 Apr;13(2):80–85. doi: 10.1111/j.1600-0676.1993.tb00611.x. [DOI] [PubMed] [Google Scholar]
  8. Kohgo Y., Kato J., Nakaya R., Mogi Y., Yago H., Sakai Y., Matsushita H., Niitsu Y. Production and characterization of specific asialoglycoprotein receptor antibodies. Hybridoma. 1993 Oct;12(5):591–598. doi: 10.1089/hyb.1993.12.591. [DOI] [PubMed] [Google Scholar]
  9. Morell A. G., Irvine R. A., Sternlieb I., Scheinberg I. H., Ashwell G. Physical and chemical studies on ceruloplasmin. V. Metabolic studies on sialic acid-free ceruloplasmin in vivo. J Biol Chem. 1968 Jan 10;243(1):155–159. [PubMed] [Google Scholar]
  10. O'Hare K. B., Hume I. C., Scarlett L., Chytrý V., Kopecková P., Kopecek J., Duncan R. Effect of galactose on interaction of N-(2-hydroxypropyl)methacrylamide copolymers with hepatoma cells in culture: preliminary application to an anticancer agent, daunomycin. Hepatology. 1989 Aug;10(2):207–214. doi: 10.1002/hep.1840100215. [DOI] [PubMed] [Google Scholar]
  11. Sawamura T., Nakada H., Hazama H., Shiozaki Y., Sameshima Y., Tashiro Y. Hyperasialoglycoproteinemia in patients with chronic liver diseases and/or liver cell carcinoma. Asialoglycoprotein receptor in cirrhosis and liver cell carcinoma. Gastroenterology. 1984 Dec;87(6):1217–1221. [PubMed] [Google Scholar]
  12. Schwartz A. L., Fridovich S. E., Knowles B. B., Lodish H. F. Characterization of the asialoglycoprotein receptor in a continuous hepatoma line. J Biol Chem. 1981 Sep 10;256(17):8878–8881. [PubMed] [Google Scholar]
  13. Torrani Cerenzia M., Fiume L., De Bernardi Venon W., Lavezzo B., Brunetto M. R., Ponzetto A., Di Stefano G., Busi C., Mattioli A., Gervasi G. B. Adenine arabinoside monophosphate coupled to lactosaminated human albumin administered for 4 weeks in patients with chronic type B hepatitis decreased viremia without producing significant side effects. Hepatology. 1996 Apr;23(4):657–661. doi: 10.1002/hep.510230401. [DOI] [PubMed] [Google Scholar]
  14. Trerè D., Farabegoli F., Cancellieri A., Ceccarelli C., Eusebi V., Derenzini M. AgNOR area in interphase nuclei of human tumours correlates with the proliferative activity evaluated by bromodeoxyuridine labelling and Ki-67 immunostaining. J Pathol. 1991 Sep;165(1):53–59. doi: 10.1002/path.1711650109. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES