Transmission and scanning electron microscopy and histochemical and biochemical methods were used to investigate differences in cell structure and cell surface properties between the strain-specific TA3-St and nonstrain-specific TA3-Ha ascites sublines of the TA3 murine mammary adenocarcinoma. The TA3-St subline is lethal only to the syngeneic strain A mouse (the strain of origin), whereas the TA3-Ha subline is lethal even to foreign species. In contrast to the TA3-St cell surface, which has numerous folds and irregular microprojections, the TA3-Ha cell has abundant long microvilli of uniform dimensions. An extensive cell surface coat which resembles the "fuzz" coat found on microvilli of normal epithelium was present on the TA3-Ha, but not on the TA3-St cells. After routine fixation, the surface coat of the TA3-Ha cell usually appeared as a filamentous network extending 30-50 nm from the plasmalemma; occasionally, longer filamentous or rod-like structures were found extending 200-400 nm from the plasmalemma. The cell coat material was more extensive on the microvilli than on the intermicrovillous membranes. Free virus-like particles associated with TA3-Ha cells have a similar-appearing surface coat on their outer membranes. The density of surface anionic sites, determined with polycationic ferritin, was greater on the TA3-Ha than on the TA3-St cell surface, consistent with the presence at the TA3-Ha cell surface of several-fold more neuraminidase-susceptible sialic acid groups. The observed surface features of the nonstrain-specific TA3-Ha cell, in comparison to the strain-specific TA3-St cell, are consistent with the suggestion that sialic acid-rich glycoproteins at the TA3-Ha cell surface mask histocompatibility antigens and enhance the ability of malignant cells to invade foreign species.

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