Structural and functional aspects of tumor cell sialomucins.

ABSTRACT

Sialomucins are abundant on the surfaces of certain ascites tumor cells and have been implicated in the escape of tumors from immune destruction and metastasis. They are large, highly glycosylated glycoproteins which are rich in serine and threonine and have a variety of 0-linked oligosaccharides. The sialomucin (ASGP-1) or 13762 rat mammary adenocarcinoma ascites cells represents more than 0.5% of the total cell protein and can be isolated from cell membranes by centrifugation in 4 M guanidine hydrochloride-cesium chloride. ASGP-1 can also be isolated from membranes or cells by nonionic detergent extraction as a 11 complex with a second glycoprotein ASGP-2. Studies with the fluorescent lectins peanut agglutinin, which binds ASGP-1, and Concanavalin A, which binds ASGP-2, indicate that the glycoproteins are present at the cell surface as a complex. ASGP-1 is shed into cell culture medium or ascites fluid, apparently by a proteolytic cleavage mechanism. 13762 ascites cells grown in culture or as solid tumors lose their ASGP-1. The sialomucin reappears with extensive passage of the tumor cells in ascites form. Studies on the biosynthesis of ASGP-1 indicate that carbohydrate is being added over nearly the entire period of transit of ASGP-1 from the site of polypeptide synthesis to the plasma membrane. The negatively charged, rod-like structure of the sialomucins suggests that they may play a role in inhibiting recognition or binding processes necessary for the immune destruction of these tumor cells.