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 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.
Pushkareva
M Y
MY
The Liposome Company, Princeton, New Jersey 08540, USA. mpushkar@lipo.com
Wannberg
S L
SL
Janoff
A S
AS
Mayhew
E
E
D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004337:Drug Carriers; D004357:Drug Synergism; D006801:Humans; D051861:Kangai-1 Protein; D008081:Liposomes; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010587:Phagocytosis / Q000187:drug effects; D010742:Phospholipid Ethers / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D011990:Receptors, Transferrin / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D020298:U937 Cells
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents; C068126:CD71 antigen; C497688:CD82 protein, human; D004337:Drug Carriers; D051861:Kangai-1 Protein; D008081:Liposomes; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D010742:Phospholipid Ethers; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014409:Tumor Necrosis Factor-alpha; C026659:edelfosine; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate