Effect of 12-O-tetradecanoylphorbol-13-acetate on colony formation and intercellular communication in a coculture system of JB6 clones.

Abstract

Disruption of intercellular communication (IC) by tumor promoters has been implicated as one of the major events in the promotion process. We studied the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on IC in relation to colony formation (CF) in a coculture system of mouse epidermal JB6 cells, including unpromotable, promotable, and transformed clones. CF was evaluated in cocultures where cells were overlaid onto irradiated mat cells. IC was evaluated by the dye transfer assay in cocultures where overlaid cells were labeled with fluorescent beads. Enhancement of CF by TPA was observed in combinations where promotable clones were used as overlays. However, suppression of IC by TPA was observed in all clones of overlaid cells (day 1) and did not correlate satisfactorily to subsequent CF. Growth-arrested cells retained their capability to communicate with mat cells, while IC between colony-forming cells and mat cells was disrupted during CF (day 5), implying that selective communication is an event secondary to CF. It is suggested that in our experimental model, short-term suppression of IC by TPA may not be sufficient to explain subsequent colony formation and that other factors should be considered.