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 non-promotable 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.