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. 1978 Dec;75(12):6049–6053. doi: 10.1073/pnas.75.12.6049

Monovalent antibodies directed to transformation-sensitive membrane components inhibit the process of viral transformation

C A Lingwood 1,2,*, A Ng 1,2,†, S Hakomori 1,2
PMCID: PMC393115  PMID: 216010

Abstract

Monovalent antibodies (Fab) directed to two classes of transformation-sensitive cell surface components, ganglioside and galactoprotein a (Gap a), inhibit the process of oncogenic viral transformation of cells. Mouse 3T3 cells infected with murine sarcoma virus were not transformed in terms of morphology change and enhancement of sugar uptake when the infected cells were cultured in the presence of monovalent antibodies directed to GM1 ganglioside or to Gap a. Transformation inhibitory activity of these cell surface ligands was not related to cell growth inhibition because the monovalent antibodies to globoside and divalent Con A were growth inhibitory but did not inhibit oncogenic transformation. Neither anti-GM1 Fab nor anti-Gap a Fab inhibited virus production. The transformation inhibitory activity of antiganglioside and anti-Gap a Fab was additionally assessed by inhibiting the transformed phenotype in NRK cell lines with mutants of avian sarcoma virus that are temperature sensitive for expression of the transformation phenotype (NRK/LA25). In this cell line, the GM3 ganglioside (not GM1) and Gap a were transformation-sensitive cell surface components. The expression at permissive temperature of transformed phenotypes, such as morphology change and capability of growth in 0.3% agar, was inhibited by preincubation of the cells with anti-GM3 Fab or anti-Gap a Fab.

GM3 labeling of NRK/LA25 cells decreased at permissive temperature, whereas preincubation of cells with anti-Gap a, which induces the inhibition of transformation after a temperature shift, prevented the decline of GM3 label on the cell surface. The data suggest a possible correlation between GM3 and Gap a expression. Application of monovalent antibodies to these transformation-sensitive components may prevent changes of these components on cell surfaces, and thus may result in abortion of phenotypic expression of transformation, although the transforming gene (src) has been set active. These results indicate that pericellular structures influence gene expression.

Keywords: gangliosides, galactoprotein a, tumor virus, phenotype

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