Release of fibronectin is linked to tumor promotion: response of promotable and non-promotable clones of a mouse epidermal cell line

By use of indirect immunofluorescence technique and enzyme-linked immunosorbent assay we show that JB 6 mouse epidermal cells have cell surface fibronectin (FN) and release FN into the culture medium. The addition of 10−8 M 12-O-tetradecanoylphorbol-13-acetate (TPA) to promotable clones caused a 2-fold enhancement of the FN release over solvent control. On the other hand, in non-promotable clones, TPA in concentrations of 10−8 M or 10−7 M did not cause increased FN release. Mezerein, a non-phorbol diterpene and second-stage tumor promoter was also found to be active in causing enhanced FN release in promotable but not in non-promotable clones. The vitamin A derivative retinoic acid (RA) antagonized the TPA-caused FN-release in promotable clones. RA had, however, no effect on the basic release patterns, when given alone or given to nonpromotable clones together with TPA. These results suggest that the increased release of FN may be a required event for promotion to transformation. Our view is derived from the observation that promotable clones of the JB 6 cell line release increased amounts of FN into their medium upon promoter exposure while non-promotable clones are unaffected.