TPA-ENHANCED INVASION OF MATRIGEL ASSOCIATED WITH AUGMENTATION OF CELL MOTILITY BUT NOT METALLOPROTEINASE ACTIVITY IN A HIGHLY METASTATIC VARIANT (L-10) OF HUMAN RECTAL ADENOCARCINOMA CELL-LINE RCM-1

We previously found that the enhanced activity to invade Matrigel upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) was one o f the major properties of a highly metastatic variant (L-10) of a huma n rectal adenocarcinoma cell line RCM-1. To clarify the mechanism of t his enhancement, we examined the effect of TPA on 2 major biological f actors involved in tumor cell invasion: cell motility and matrix-degra ding metalloproteinase activity. The enhanced invasiveness was inhibit ed by protein-kinase-C inhibitors. TPA markedly enhanced both haptotac tic response to type-IV collagen and motility on tissue-culture glass substrate of L-10 cells in a dose-response manner quite similar to tha t of TPA-enhanced invasion of Matrigel. On the other hand, TPA showed little enhancement of metalloproteinase production, which was assessed by gelatin- and casein-zymography, and of type-IV collagenolytic acti vity. Addition of TIMP (tissue inhibitors of metalloproteinase)-1 inhi bited TPA-enhanced invasion of Matrigel by only up to 13%. Thus, TPA t reatment of L-10 cells enhanced invasion of Matrigel in association wi th augmentation of cell motility but did not enhance metalloproteinase activity. (C) 1993 Wiley-Liss, Inc.