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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2000-01, Vol.48 (10), p.569-578
• Main Authors: PUSHKAREVA, M. Y, WANNBERG, S. L, JANOFF, A. S, MAYHEW, E
• Format: Article
• Language: English
• Subjects: 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine; Antigens, CD - biosynthesis; Antigens, Differentiation, B-Lymphocyte - biosynthesis; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; CD11b antigen; CD71 antigen; Cell Differentiation - drug effects; Drug Carriers; Drug Synergism; General aspects; Humans; Kangai-1 Protein; lamins; Liposomes; Lymphoma, Large B-Cell, Diffuse - metabolism; Macrophage-1 Antigen - biosynthesis; Medical sciences; Membrane Glycoproteins - biosynthesis; Original; Phagocytosis - drug effects; Pharmacology. Drug treatments; Phospholipid Ethers - pharmacology; poly(ADP-ribose) polymerase; Proto-Oncogene Proteins; Receptors, Cell Surface - biosynthesis; Receptors, Transferrin - biosynthesis; Tetradecanoylphorbol Acetate - pharmacology; transferrin receptors; Tretinoin - pharmacology; Tumor Necrosis Factor-alpha - biosynthesis; U937 Cells
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/PL00006675

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 alpha-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 alpha production by U-937 cells.