Changing tumour antigen expression in metastatic hepatocellular carcinoma cells of the guinea pig

Summary  Hepatocellular carcinoma cells (Line-10), obtained from ascitic fluid after diethylnitrosamine treatment of Sewall Wright strain-2 guinea pigs, produce solid (primary) tumours, lymphnode and lung metastases and malignant ascites when reinjected into animals of the same strain. Monoclonal antibodies were raised against the tumour cells by immunizing BALB/c mice with viable ascitic hepatocellular Line-10 tumour cells. Three hybridomas producing anti-Line-10 monoclonal antibodies were selected for further studies (10TL1, 10TL40 and 10TL43) and compared with monoclonal antibodies against intermediate filament keratins. The anti-Line-10 monoclonal antibodies did not cross react with Line-1 hepatocellular carcinoma cells, nor with normal guinea pig hepatocytes. When ascitic Line-10 cells form high papillary projections on the peritoneal surface, they significantly reduced their antigen expression of 10TL40 and of 10TL43 defined antigens, while the expression of 10TL1 defined antigens remained unaltered. Invading Line-10 cells in the deep submesothelial stromal tissue, however, lost reactivity with MoAb 10TL43 but not with the MoAb’s 10TL40 and 10TL1. The antigens on lung- and lymphnode metastases remained largely unaffected. The reactivity with MoAb’s 10TL40 and with 10TL43 was also lost upon prolonged culturing of Line-10 cells. The reactivity of Line-10 and Line-1 cells with all monoclonal antibodies against keratin filaments remained unaltered. Line-1 cells could be distinguished from Line-10 cells by the absence of any reactivity with the MoAb’s 10TL1, −40, −43, but also by the fact that 100% of the Line-1 cells were positive with antibodies against keratins 5/8, 18, and 7. The majority (>90%) of Line-10 cells, however, did not express the keratin 7. Since keratin 7 was also absent from guinea pig hepatocytes but strongly present on liver bile ductules it is suggested that the different antigenic make up of Line-1 and Line-10 cells might be related to a distinct cellular origin within the liver.