Characterization of in vitro immunoselected variants from a highly metastatic murine tumor for alterations in malignant behavior in vivo.

ABSTRACT

A new Ly-6.2- antigen-loss variant (called L61 -M1) of the highly metastatic DBA/2 mouse (Ly-6.2+) MDAY-D2 tumor has been obtained by means of a monoclonal anti-Ly-6.2 antibody in an in vitro immunoselection technique. Whereas L61 -M1 grew poorly when inoculated subcutaneously into the syngeneic host, it grew and metastasized in a similar way to the parental MDAY-D2 tumor when inoculated into immunosuppressed, athymic nude mice. L61 -M1 as well as another Ly-6.2- variant of the same MDAY-D2 tumor (called L61 ) which is poorly metastatic in the syngeneic host salvaged exogenous fucose into glycoproteins and glycolipids at rates 5.5 and 7.8 times that of the parental MDAY-D2 line. In contrast, the Ly-6.2- variants exhibited a 50-70% decrease in the incorporation of exogenous mannose into glycoproteins and glycolipids. L61 -M1 and L61 also exhibited alterations in the structures of the oligosaccharide moieties linked to the cell surface glycoproteins and/or glycolipids. Thus, the in vitro immunoselection technique can be used to obtain a panel of variants with stable phenotypic alterations in their growth and metastatic capacities. Such mutants may, like previously described lectin-resistant mutants, be useful in studying the contribution of cell surface glycoproteins and glycolipids to tumorigenicity and metastasis.