The target site of adhesion-blocking Fab in aggregating Dictyostelium cells is a plasma membrane glycoprotein of approximate molecular weight 82,000 (refs 1--3), which is no longer synthesized after aggregation, and disappears from the plasma membrane. However, since cell adhesion remains important during later stages of differentiation, presumably important during later stages of differentiation, presumably another proteins(s) takes over its function. One candidate is a glycoprotein (molecular weight 95,000) whose synthesis commences at the tip stage and continues until the completion of development. Both proteins are strongly antigenic. When pseudoplasmodia ('slugs', a late developmental stage) are disaggregated and replated, the cells recapitulate the previous sequence of morphological changes much more quickly than before, although the glycoprotein of molecular weight 82,000 is not resynthesized during reaggregation. We report here that monovalent antibody (Fab) directed against slug plasma membranes inhibits reaggregation by binding to the glycoprotein of molecular weight 95,000 which thus seems to be involved in cell adhesion.

Abercrombie's confronted explant technique was used to study the role of tumor surface antigens in malignant invasion. Plasma membranes were isolated from mouse sarcoma cells (FS9) and a mouse cell line (L929) of the same H-2 haplotype. FS9 cells are highly invasive when confronted with chicken heart fibroblasts, whereas the L929 cells are not [Abercrombie, M. (1979) Nature (London) 281, [259][260][261][262]. The FS9 plasma membranes contained significantly higher concentrations of a 37,00O-dalton glycoprotein. When antiserum directed against FS9 plasma membranes was preabsorbed with L929 cells, the antibodies remaining reacted predominantly with the 37,000-dalton antigen. Fab fragment prepared from the preabsorbed antiserum inhibited the invasion of chicken heart fibroblasts by FS9 cells. Fab prepared from a monoclonal antibody directed against the 37,000-dalton antigen also inhibited invasivity, whereas monoclonal antibodies reacting with two other FS9 cell surface antigens did not. The results imply a relationship between the increased concentration of the 37,000-dalton glycoprotein on the surface of the FS9 cells and their invasivity.The surfaces of tumor and normal cells are believed to differ in one or more significant aspects (1). Metastasis involves detachment of cells from the pnmary tumor, their adhesion to vascular endothelia at distant sites, invasion of the vessel wall, and growth in the stroma (1, 2). The ability of metastatic cells to participate in cell-cell and cell-endothelial matrix interactions may be associated with their invasive properties. Hence, tumor cell-surface proteins may mediate metastasis and, in fact, fusion of membrane vesicles can transfer the potential for a higher rate of metastasis to poorly metastatic sublines (3). However, attempts to detect qualitative differences in surface properties between cells with different metastatic potential have been inconclusive (1-7). Studies using mouse B16 melanoma metastatic variants suggested that differences in surface proteins may be related to greater protease or glycosidase activity in cells with lower metastatic potential (8). Recently, some of the monoclonal antibodies that blocked adhesion of B16 cells to tissue culture dishes were also found to reduce formation of metastases in vivo (9). The antibodies were directed against antigens on the surface of B16 but not normal mouse cells.We chose to use the Abercrombie confronted explant technique to study the role of surface proteins in the invasive behavior of malignant cells (10)(11)(12)(13). In this technique an explant of malignant cells is confronted with a standardized chicken heart explant. The mouse sarcoma (FS9) cells we selected to study show nonreciprocal invasion (13). When the outgrowths of the two explants meet, the chicken heart fibroblasts are almost totally obstructed, whereas the outward drive of the FS9 explant persists into the fibroblast explant's zone. The mouse cell line L929 was selected as a control because these cells show a high degree of obstruction w...

Monoclonal antibodies against the mouse sarcoma FS9 were prepared. Antibodies recognizing a 37,000 dalton glycoprotein on FS9 tumor cells inhibit invasion by FS9 sarcoma cells of chicken heart fibroblasts in vitro as assessed by Abercrombie's confronted explant assay. Antibodies to other membrane proteins of FS9 tumor cells failed to inhibit invasiveness of FS9 sarcoma cells. The 37,000 dalton glycoprotein, which is neither a histocompatibility antigen nor a gp37 glycoprotein of Rous sarcoma virus nor the MEP described by Gottesman, is present on the surface and in the cytoplasm of FS9 sarcoma cells. The plasma membrane of the non-invasive mouse cell line L929 contains only low concentrations of the 37,000 dalton antigen. Hence, a relationship apparently exists between the increased concentration of this protein on the surface of FS9 cells and their invasiveness.

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