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Three factors may be responsible for the sharp difference in tumourigenicity between cloned murine fibrosarcoma lines maintained in vitro, and cells of the same lines after in vivo passage, initially in a T cell deficient mouse and subsequently in normal mice: (1) acquisition during passage of resistance to NC cells; (2) acquisition during passage of a surface molecule, probably a sialic acid, which protects the cell against T cell-mediated lysis; and (3) ability of the passaged cells, but not the non-passaged cells, to produce sufficient amounts of autocrine growth factors necessary for growth in vivo. The tumourigenicity of the passaged cells cannot be attributed to failure to express TATA or MHC class I molecules.