Monoclonal antibodies reacting with normal rat liver cells as probes in hepatocarcinogenesis

• Published in: Cancer research (Chicago, Ill.) Vol. 44; no. 4; pp. 1611 - 1624
• Main Authors: HOLMES, C. H, AUSTIN, E. B, FISK, A, GUNN, B, BALDWIN, R. W
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.1984
• Subjects: Animals; Antibodies, Monoclonal; Antigen-Antibody Complex; Antigens, Neoplasm - analysis; Antigens, Surface - analysis; Biological and medical sciences; Epitopes - analysis; Gastroenterology. Liver. Pancreas. Abdomen; Immunoenzyme Techniques; Liver - immunology; Liver Neoplasms - chemically induced; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Liver Neoplasms, Experimental - immunology; Liver Regeneration; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; p-Dimethylaminoazobenzene; Rats; Rats, Inbred Strains; Tumors; Rat; Liver; Rodentia; Monoclonal antibody; Hepatobiliary disease; Carcinogenesis; Carcinogen; Vertebrata; Mammalia; Hepatocyte; Immunological investigation; Liver cell carcinoma; Digestive diseases; Experimental tumor
• ISSN: 0008-5472; 1538-7445

A series of four monoclonal antibodies was raised against suspensions of normal adult WAB/Not rat hepatocytes. An immunoperoxidase-staining technique was used to examine the distribution of determinants detected by these antibodies on frozen sections of fetal, neonatal, adult, and regenerating liver and on a range of 4-dimethylaminoazobenzene-induced liver lesions, including a panel of 32 primary liver carcinomas. Three of the antibodies were directed against hepatocytes, while a fourth antibody stained stromal elements within the liver. The determinants detected by the anti-hepatocyte monoclonal antibodies arose in a specific sequence during normal liver development and, when assessed in conjunction, characterized several phenotypes associated with stages in normal hepatocyte differentiation. These same antibody-defined phenotypes were expressed by the primary liver carcinomas, and the distribution of phenotypes among the tumors revealed a heterogeneity which was not evident from a conventional morphological classification. Primary liver tumors expressed a total of four antibody-defined phenotypes, whereas gamma-glutamyl transpeptidase-positive foci of hepatocytes and neoplastic nodules expressed, respectively, only one or 2 antibody-defined phenotypes. We suggest that monoclonal antibodies directed against normal liver cell components may provide a means to establish lineage relationships between cell populations involved in hepatocarcinogenesis.