ULTRASTRUCTURAL-STUDY OF TPA-INDUCED CELL MOTILITY - HUMAN WELL-DIFFERENTIATED RECTAL ADENOCARCINOMA CELLS MOVE AS COHERENT SHEETS VIA LOCALIZED MODULATION OF CELL-CELL ADHESION

We previously found that 12-O-tetradecanoylphorbol-13-acetate (TPA)-en hanced invasion of Matrigel was associated with augmentation of cell m otility but not with metalloproteinase activity in a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1. In a t wo-dimensional cell motility assay, TPA induced active L-10 cell locom otion with characteristic morphology; the cells moved outwards from th e cell islands mainly as a localized coherent sheet of cells. The lead ing cells showed locomotor morphologies with fan-shaped leading lamell ae while the following cells had cell contacts on all sides and appear ed to lack leading lamellae. In the present ultrastructural study, the following cells frequently showed tapering cytoplasmic protrusions an d leading lamella-like processes underlapping a preceding cell, indica ting that the locomotion mechanism is almost the same for both the lea ding and following cells. For this type of locomotion as a coherent sh eet we propose that localized modulation of cell-cell adhesion was ind uced such that wide intercellular gaps occurred at the lower portion o f the cells to allow the cells to extend the tapering cytoplasmic proc esses and leading lamellae while close cell-cell contacts remained at the upper portion of the cells. These TPA-induced changes took place p redominantly in the cells at the periphery of the cell islands, while the cells in the middle of the cell islands maintained close cell-cell contacts including complex interdigitation all around the cells, sugg esting the modulation of TPA action by cell-cell interaction. Addition ally, consistent with the evidence for junctional complexes between th e cells moving outwards, the Lucifer-yellow dye transfer studies showe d some, limited cell-cell coupling, suggesting the presence of at leas t some gap junctional intercellular communication in the moving cell s heets.