Abstract

To study the early steps of invasion in vitro, spheroidal aggregates of invasive mouse fibrosarcoma cells (MO4) were confronted with precultured fragments of embryonic chick heart. The confronting tissues attached to one another within 45 min of incubation at 37° C. Photo- and electron microscopy indicate that attachment is brought about by extensions from MO4 cells penetrating between the peripheral fibroblastic cells of the heart fragment. Formation of such extensions appears to be triggered by immediate contact of the MO4 cells with the heart tissue. Attachment did not occur at 4° C, and the rate of attachment at 37° C was lowered by KCN, indicating an active cellular process depending on ATP energy. Cytochalasin B also lowered the rate of attachment, whereas cycloheximide had no significant effect. The latter measurements and the ultrastructure of the extensions suggested that bundling of microfilaments was involved in the attachment. Nocodazole at doses which prevented assembly of cytoplasmic microtubules, like 5-fluorouracil and ionizing radiation at doses which inhibited the growth of the MO4 aggregates but left the cytoplasmic microtubular complex intact, hardly influenced the rate of attachment. These experiments indicated that attachment resulted from random motility, contrary to further steps of invasion which were shown to depend on directional migration.

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