Human pancreatic adenocarcinoma-associated antigens defined by novel murine monoclonal antibodies Pak-1 and Pak-2

Summary

Two murine monoclonal antibodies (MoAbs) Pak-1 and Pak-2 were established by immunizing Balb/c mice with human pancreatic adenocarcinoma xenografts, previously established in mice. Pak-1 showed a strong positive immunostaining to well- and moderately-differentiated tubular duct cell carcinoma of the pancreas but neither to poorly-differentiated nor to other non-tubular pancreatic carcinomas. Pak-2 showed a wide spectrum of immunostaining to ductal and islet cell carcinomas of the pancreas, revealing less reactivity to well-differentiated tubular duct cell carcinomas than Pak-1. The broad specificity of Pak-2 was similarly observed with extrapancreatic tumor tissues. Neither normal pancreatic tissues nor those with chronic pancreatitis were stained with Pak-1 and Pak-2, whereas the islet cells of normal pancreas were stained by both of them. Western blot analysis revealed that Pak-1 recognized two distinct glycoprotein molecules of ductal adenocarcinoma, 100K dalton molecular weight (MW) and pH6-7 isoelectric points (IP) on two dimensional electrophoresis, and that Pak-2 recognized three glycoprotein molecules, 35K dalton MW and pH7-10 IP. The treatment with periodic acid, neraminidase, trypsin and pronase revealed that antigenic epitopes of Pak-1 and Pak-2 may be composed of complex polysaccharide structure rather than terminal sialic acid residues.