A new murine fibrosarcoma model has been developed in which it is possible to compare in vitro the behaviour of tumour cells with that of normal parental cells from which the tumour was originally derived by spontaneous transformation in vitro. Tumour cell lines were obtained which showed differing capacities for localized invasion of the skin following subcutaneous injection: these were categorized as either highly invasive or poorly invasive and were compared with the normal cells for (I) their respective saturation densities when grown on plastic, (2) their ability to grow in agar, and (3) their secretions of the metalloenzyme collagenase and the specific inhibitor of metalloproteinases (TIMP). Although increased in vitro saturation density showed some correlation with increased invasiveness in vivo, the most striking correlation was the 10- to 20-fold reduction in TIMP secretion by tumour cells of high invasive potential compared with normal cells or tumour cells with low invasive potential. No collagenase secretion by tumour cells was ever detected. It is proposed that local TIMP levels may play a crucial in the control of tumour invasion in vivo.
The effect of interferon (IFN) on a series of cellular properties which characterize the transformed state was studied, using normal mouse fibroblasts (both established lines and embryo cells) and cloned derivatives transformed by murine sarcoma virus. It was found that the transformed cells behaved in a more normal fashion in the presence of IFN. This was indicated by reduction in saturation density, decreased DNA synthesis in crowded cultures, decreased formation of foci on monolayers of normal cells, and decreased growth in soft agar. These effects were not due to generalized inhibition of cell growth, since IFN had little effect on the growth and cloning efficiency of the cells used. In the presence of IFN, cellular morphology also appeared more normal. These results suggest that growth control of transformed cells may be at lease partly restored by IFN, an effect which could in part account for the anti-tumour effect of IFN
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