A fibrosarcoma model derived from mouse embryo cells: growth properties and secretion of collagenase and metalloproteinase inhibitor (TIMP) by tumour cell lines.

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.