Faculty Bibliography

Plasminogen activator secretion by 39 primary or early-passage cultures of malignant human neoplasms has been compared with that of 16 similar cultures of benign neoplasms and 39 cultures of normal or reactive tissue. While normal cells of mesenchymal or neural origin secreted considerably less plasminogen activator than did cells from frankly malignant tissues, elevated levels of enzyme secretion were also encountered in cultures of benign neoplastic or reactive cells. In the case of epithelial tissue, no consistent relationship between plasminogen activator secretion and neoplasia could be documented. Our failure to observe, for any particular cell type, a reproducible correlation between malignancy and plasminogen activator secretion may be attributable to the artificial conditions of in vitro culture, where normal in vivo regulatory mechanisms do not obtain

This paper reports the effect of vitamin A and its derivatives, the retinoids, on plasminogen activator (PA) synthesis in chick embryo fibroblast cultures (CEF). Low concentrations of retinoic acid (RA) (10(-6)-10(-10) M) and the retinoids stimulated PA synthesis in CEF; the maximal stimulation achieved, 9--10 fold, was somewhat lower than that obtained with optimal concentrations of the potent tumor promoter phorbol myristate acetate (PMA). This action of RA required protein and mRNA synthesis but, in contrast to enzyme induction by PMA and/or sarcoma virus transformation, retinoid effects were not significantly inhibited by elevated concentrations of cAMP. In inducing and/or stimulating PA production, the effects of RA and sarcoma virus transformation were synergistic rather than additive. Analogous synergism was observed between RA and PMA, but only at suboptimal concentrations of the latter. RA did not affect PA production in normal or transformed cultures maximally stimulated by PMA. These findings may help to elucidate the role of retinoids in promoting tumor growth, tissue remodeling and teratogenesis