TUMOR-NECROSIS-FACTOR-ALPHA INDUCES THE EXPRESSION OF CARBONIC-ANHYDRASE-II IN PANCREATIC ADENOCARCINOMA CELLS

TNF is a 17kD cytokine classically known for its cytotoxic effects on malignant cells. More recent cell culture studies demonstrated TNF ind uced cytostasis associated with the expression of a terminally differe ntiated phenotype. This was best characterized in malignant hematopoie tic models, although a similar action on cells derived from solid tumo rs is now increasingly recognized. In the present study, six day expos ure to TNF (40 ng/ml) stimulated morphologic changes in a human pancre atic adenocarcinoma cell line (HPAC), including increased cellular hom ogeneity, decreased nuclear to cytoplasmic ratio and detachment from t he cell monolayer. Proliferation and DNA synthesis were reversibly inh ibited while cellular viability was maintained. Parallel to the change s in morphology and growth was the delayed appearance of carbonic anhy drase II. (CA II, E.C. 4.2.1.1), an accepted marker for pancreatic cel ls of ductal origin. A concomitant increase in the steady-state level of CA II mRNA was also observed over the time-course of TNF exposure. These results suggest a novel role for TNF in the induction of a more terminally differentiated ductal eel phenotype in a human pancreatic c arcinoma model. (C) 1994 Academic Press, Inc.