MODIFICATION OF THE ERYTHROCYTE SURFACE IN RATS BEARING YOSHIDA ASCITES SARCOMA IS BROUGHT ABOUT BY A TUMOR VARIANT OF ALPHA(2)-MACROGLOBULIN

Erythrocytes from the circulation of rats bearing Yoshida ascites sarc oma,exhibit higher concanavalin A (ConA)-mediated agglutinability than those from normal animals. A tetrameric glycoprotein of subunit molec ular mass 170 kDa, purified from the cell-free ascites fluid, was foun d to confer higher ConA-mediated agglutinability on erythrocytes in vi tro. An antiserum to this tumour-derived protein failed to detect any cross-reactive component in normal rat plasma or in any of the normal tissues examined. An immunoreactive protein was, however, detected in blood plasma when the acute-phase reaction was stimulated by injection of turpentine. The cross-reactive acute-phase protein was purified by ConA-affinity, gel-filtration and ion-exchange chromatography, and id entified as alpha(2)-macroglobulin. The acute-phase protein and the pr otein obtained from the ascites fluid have identical or very similar n ative and subunit molecular masses, subunit arrangement and pI. They b oth are able to inhibit trypsin and, as a consequence, acquire greater mobility in native PAGE. In addition, the two proteins bind to rat er ythrocytes non-specifically, and in similar amounts. However, despite these similarities, the acute-phase protein is unable to enhance the a gglutinability of erythrocytes. The two proteins differ in their carbo hydrate content, but this differential glycosylation is not the cause of the difference in their surface modification activity. The chemical ly deglycosylated proteins show a small but consistent difference in t he size of their polypeptides. Their tryptic peptide maps, although la rgely similar, show some differences, as do their amino acid compositi ons. It is probable that the proteins are independent members of the s ame (alpha-macroglobulin) family. The rat embryo is also found to expr ess a soluble protein consisting of a 170 kDa polypeptide that crossre acts with the antibody to the tumour-derived protein. The purified emb ryo protein is able to alter the ConA-mediated agglutinability of eryt hrocytes in vitro, and also yields a tryptic peptide map that is ident ical to that of the tumour-derived protein. The modification of the ho st cell surface in the tumour-bearing rats is thus caused by what appe ars to be a tumour(oncofetal?) variant of alpha(2)-macroglobulin.