PHARMACOLOGICAL ALTERATIONS OF CELLULAR TRANSGLUTAMINASE ACTIVITY ANDINVASIVENESS IN HUMAN COLORECTAL-CARCINOMA CELLS

Human colorectal tumor cells expressing differing metastatic potential and tissue transglutaminase (TGA) activity were tested for the abilit y of various pharmacological agents to enhance TGA activity. The most effective stimulant was tetradecanoylphorbol-13-acetate (TPA), which i n human colon carcinoma cells (SW620) caused a 5-fold, protein synthes is dependent increase in activity over 3 days. In WiDr and SW480 cells TGA activity was less susceptible to induction by TPA, possibly owing to the higher basal levels of TGA. Retinoic acid and a synthetic reti noid, {RO 15-1570; halene-2-yl)propen-1-yl[benzenesulphonyl-ethane)}, also induced TGA activity to a lesser extent in SW620 cells, whereas o ther differentiation inducers {sodium butyrate and hexamethylene bis-a cetamide (HM[BA)} were ineffective. In LS174T cells, TGA activity was resistant to induction by all of the agents. The synthetic retinoid (R O 15-1570) inhibited in vitro invasiveness of SW620 cells, however, TP A treatment or addition of exogenous TGA did not inhibit invasiveness of these cells. Hence, the invasive behavior of a metastatic human col on tumor cell line (SW620) does not appear to be dependent on the TGA activity which the cells express. The anti-invasive activity of the re tinoid in SW620 cells therefore may be mediated by some other mechanis m.