PROSTAGLANDIN E(2) DOWN-REGULATES THE EXPRESSION OF HLA-DR ANTIGEN INHUMAN COLON ADENOCARCINOMA CELL-LINES

Prostaglandins (PG) have been implicated in the pathogenesis of cancer and play an important role in immune regulation. Colon cancer is asso ciated with elevated levels of PGE(2), while aspirin, the prototypical inhibitor of PG synthesis, appears to reduce the incidence of colon c ancer by 50%. We have observed that in human colon cancer the expressi on of HLA class I and LI antigens is reduced or lost; loss of HLA anti gens is suspected to be a mechanism by which the malignant cell escape s the immune surveillance. We investigated the effect of these eicosan oids on the expression of HLA antigens in human colon adenocarcinoma c ell lines. PGE(2) down-regulated the expression of the class II antige n HLA-DR in SW1116 cells (65% reduction at 2.8 x 10(-8) M). This effec t was dose- and time-dependent, reversible, and specific (PGF(2 alpha) and LTB(4) had no effect; the expression of carcinoembryonic antigen and class I genes were not affected). Aspirin induced the expression o f HLA-DR in HT29 cells, a cell line not expressing constitutively HLA- DR. The reduction of HLA-DR by PGE(2) was accompanied by reduced messe nger RNA (mRNA) levels of HLA-DR alpha and reduced transcription of th e corresponding gene. In contrast to HLA-DR, none of these three eicos anoids affected the expression of KLA class I genes, as assessed via d etermination of protein expression by fluorescence flow cytometric ana lysis and evaluation of the corresponding class I mRNA levels. We conc lude that PGE(2) specifically down-regulates the expression of HLA-DR, while it does not affect the expression of class I antigens. These fi ndings may be relevant to the general problem of immune surveillance o f cancer and the mode of action of aspirin in protecting from colon ca ncer.