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Invasion of malignant cells into cultured embryonic substrates.

To study malignant invasion, we associated tissue and cell culture fragments, with adhesive and non-adhesive living substrates in vitro (11). Non malignant mesonephros, quail heart and BHK-cells, as well as malignant HeLa-, Hepatoma-, Harding-Passey melanoma-, Py-, TLX5 lymphoma- and Schmidt-Ruppin sarcoma cells, were transplanted into cultured organ fragments of chick embryos and chick blastoderms. Malignant invasion was evaluated on the basis of the following histological criteria: 1. changes in organization of the graft. 2. infiltration of cells from the graft into the substrate, 3. degenerative alterations of the substrate. It was shown that adhesion of the graft to the substrate is a prerequisite for malignant invasion. Invasion into non-adhesive substrates, such as the apical side of epithelia, was never observed. Contrary, all malignant cells did invade into adhesive substrates. Interposition of a vitelline membrane always inhibited the expression of invasiveness. The morphological pattern of invasion depended mainly on the architecture of the substrate and differential resistance of its various components explained well all histological pictures. From the latter observation and from the localization of degenerative changes in the substrate we inferred that malignant cells exert their deleterious effect most probably upon immediate contact with their host.