Increased cell-surface receptor expression on U-937 cells induced by 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine

Association of the ether lipid, 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH₃) with liposomes (ELL-12) reduces acute toxicity while maintaining or enhancing anticancer activity in experimental tumor models. ELL-12 has been shown to induce apoptosis by a cytochrome-c-dependent caspase-mediated pathway, which results in proteolytic cleavage of poly(ADP-ribose) polymerase and lamins, but the antitumor effects of ET-18-OCH₃ or ELL-12 could result from tumor cell differentiation or activation. Here we compared the effects of ET-18-OCH₃ and ELL-12 on the expression of cell-surface proteins associated with cell differentiation and/or activation in U-937 cells. Phorbol 12-myristate 13-acetate and all-trans-retinoic acid, which induce differentiation in U-937 cells, up-regulated CD11b (MAC1 α-integrin) and CD82 and down-regulated CD71 (transferrin receptor) in a time- and dose-dependent manner. In contrast, ET-18-OCH₃ and ELL-12 up-regulated both CD71 and CD11b and did not have any effect on expression of CD82 in U-937 cells, suggesting that the ELL-12 may activate these cells rather than induce differentiation. Further evidence of activation was that ET-18-OCH₃ and ELL-12 strongly induced tumor necrosis factor α production by U-937 cells. Received: 25 February 1999 / Accepted: 4 August 1999