SIALOMUCIN COMPLEX, A HETERODIMERIC GLYCOPROTEIN COMPLEX - EXPRESSIONAS A SOLUBLE, SECRETABLE FORM IN LACTATING MAMMARY-GLAND AND COLON

Ascites 13762 rat mammary adenocarcinoma cells express abundantly on t heir cell surfaces a heterodimeric glycoprotein complex composed of a sialomucin ascites sialoglycoprotein (ASGP)-1 and a transmembrane subu nit ASGP-2, The latter, which contains two epidermal growth factor-lik e domains, binds the receptor tyrosine kinase p185(neu), suggesting th at the complex is bifunctional as well as heterodimeric. Immunoblot an alyses using monoclonal antibodies prepared against the complex demons trate high levels of expression in rat lactating mammary gland and col on, Immunolocalization studies with anti-ASGP-2 indicate that ASGP-2 i s present in these two tissues in the apical regions of secretory epit helial cells, Both mammary gland and colon contain a soluble, secretab le form of ASGP-2, which is not found in the ascites cells; milk and m ammary gland also have the membrane form. Immunoblot analyses using a COOH-terminal-specific polyclonal antibody indicate that the soluble f orm of ASGP-2 is missing its COOH-terminal domains, Both the soluble a nd membrane forms of ASGP-2 are similar to the membrane-associated for m from the 13762 adenocarcinoma with respect to M(r), antigenicity, an d association with ASGP-1. The presence of ASGP-1 in milk suggests tha t it is a candidate for the uncharacterized high M(r) milk mucin, MUCX , ASGP-2 expression is up-regulated in mammary gland during pregnancy, because it is undetectable in virgin and early pregnant rats but abun dant in the gland from late pregnant and lactating animals. However, c ompared with the lactating mammary gland, the 13762 ascites cells over express ASGP-2 by more than 100-fold, which may contribute to their ma lignancy. These combined results indicate that sialomucin complex is a unique secreted product in the mammary gland and colon, whose behavio r is different from that in the mammary ascites tumors, and which may play important roles in mammary and intestinal physiology.