We have previously described
a factor(s) produced by 8387
fibrosarcoma cells, which can affect
plasminogen activator (PA) activity of cultured cells. Since then,
transforming growth factor-beta (
TGF beta) has been established as a major
growth factor/
growth inhibitor that regulates both the expression and activity of PAs and their endothelial-type inhibitor (PAI-1). The present study was undertaken to characterize the 8387
fibrosarcoma cell-derived factor(s) and to investigate its relationships to
TGF beta by analysis of modulation of PA activity and cell growth. The
fibrosarcoma cell-derived
proteins were partially purified from serum-free
conditioned culture medium using Bio-Gel P-10 chromatography. Two separate fractions with apparent molecular weights of 16,000 and 12,000 contained activities that both decreased the secretion of PA activity by human lung fibroblasts and inhibited the soft
agar growth of A549
lung adenocarcinoma cells. Both factors affected similarly the production of
urokinase-type PA and
PAI-1 in various cell lines and enhanced anchorage-independent growth of murine AKR-2B fibroblasts. The effects of these factors thus resembled those of
TGF beta. The immunological relationships between the Mr 16,000 and Mr 12,000 factors and
TGF beta were therefore studied using neutralizing anti-
TGF beta antibodies. The
TGF beta antibodies efficiently inhibited the effects of the Mr 16,000 factor but not those of the Mr 12,000 factor in cell culture assays. The results suggest that 8387
fibrosarcoma cells produce two major
growth inhibitors, one of which is closely related to
TGF beta.