Cancer Metastasis Cancer Cell Lines Selected in an Animal Model for Colon Cell Surface Sialoprotein Alterations in Metastatic Murine Colon

Alterations in cell surface proteins and glycoproteins may play a key role in determining the metastatic behavior of tumor cells. The cell surface proteins of a series of related murine colon cancer cells selected in an animal model for colon cancer metastasis (R. S. Bresalier et al., Cancer Res., 47:1398-1406, 1987) were therefore compared by a variety of biochemical methods. Lactoperoxidase-catalyzed iodination of cell surface proteins followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated quantitative and qualitative differences in the cell surface protein profiles of parental cell line 51B (low metastatic potential) and its metastatic derivatives SIB l.iM 5 and 51B l .iM 6. Labeling of sialic acid-containing proteins suggested that, in the case of at least four of these proteins (M, 170,000,120,000,95,000, and 55,000), this represented an increase in radioactive labeling of sialoglycoproteins from the metastatic lines. Affinity chromatography of solubili/ed ' ""Ilabeled cell membrane proteins revealed a 2to 3-fold increase in wheat germ agglutinin and Sambucas nigra lectin binding associated with the metastatic lines, compared to the poorly metastatic parent. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of material eluted from these columns demonstrated enhancement of proteins from the metastatic cells corresponding in molecular weight to the previously identified major sialoglycoproteins. Neuraminidase-releasable mem brane-associated sialic acid and sialyltransferase activities were 2to 3fold higher in the metastatic cell lines compared to the parental line. Liver colonization after intrasplenic injection of the various lines into syngeneic mice was dramatically reduced by prior removal of cell surface sialic acid. Immunohistochemical staining of primary and metastatic tumors formed after cecal injection of parental 51B suggested selective metastasis by wheat germ agglutinin-binding tumor cells. These results further support the concept that cell membrane sialylation is important in determining the metastatic potential of cancer cells.