This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Utsugi, T. Articles by Fidler, I. J. Search for Related Content PubMed PubMed Citation Articles by Utsugi, T. Articles by Fidler, I. J.

Elevated Expression of Phosphatidylserine in the Outer Membrane Leaflet of Human Tumor Cells and Recognition by Activated Human Blood Monocytes¹

Department of Cell Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

We determined whether the presence of phosphatidylserine (PS) in the outer membrane leaflet of human tumor cells correlated with their recognition by activated human monocytes. Three tumorigenic cell lines, A375 melanoma and A431 and Colo-16 carcinomas, and a normal human epidermal keratinocyte line (NHEK) were incubated with monocytes activated to the tumoricidal state by -interferon and lipopolysaccharide. Activated human monocytes bound to and lysed all tumorigenic targets, while the nontumorigenic NHEK were neither bound nor killed. Semiquantitative analysis of PS in the outer leaflet of the cells revealed that the tumorigenic cells expressed 3–7-fold more PS than did the nontumorigenic NHEK. To determine whether enhanced PS expression on the tumor cells was responsible for their recognition by activated monocytes, NHEK were supplemented with exogenously supplied analogues of PS and phosphatidylcholine. PS-labeled NHEK but not phosphatidylcholine-labeled nor control NHEK bound to activated human monocytes. These results suggest a role for PS in monocyte recognition of tumor cells.

¹ Supported in part by Grants R35-CA 42107 and CA 47845 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at the Department of Cell Biology, Box 173, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 3/18/91. Accepted 4/15/91.

This article has been cited by other articles:

				V. Held-Kuznetsov, S. Rotem, Y. G. Assaraf, and A. Mor Host-defense peptide mimicry for novel antitumor agents FASEB J, December 1, 2009; 23(12): 4299 - 4307. [Abstract] [Full Text] [PDF]

				T. L. Romanuik, T. Ueda, N. Le, S. Haile, T. M.K. Yong, T. Thomson, R. L. Vessella, and M. D. Sadar Novel Biomarkers for Prostate Cancer Including Noncoding Transcripts Am. J. Pathol., December 1, 2009; 175(6): 2264 - 2276. [Abstract] [Full Text] [PDF]

				H. P. Dong, A. Holth, L. Kleinberg, M. G. Ruud, M. B. Elstrand, C. G. Trope, B. Davidson, and B. Risberg Evaluation of Cell Surface Expression of Phosphatidylserine in Ovarian Carcinoma Effusions Using the Annexin-V/7-AAD Assay: Clinical Relevance and Comparison With Other Apoptosis Parameters Am J Clin Pathol, November 1, 2009; 132(5): 756 - 762. [Abstract] [Full Text] [PDF]

				X. Qi, Z. Chu, Y. Y. Mahller, K. F. Stringer, D. P. Witte, and T. P. Cripe Cancer-Selective Targeting and Cytotoxicity by Liposomal-Coupled Lysosomal Saposin C Protein Clin. Cancer Res., September 15, 2009; 15(18): 5840 - 5851. [Abstract] [Full Text] [PDF]

				S. Vuorenoja, B. P. Mohanty, J. Arola, I. Huhtaniemi, J. Toppari, and N. A Rahman Hecate-CG{beta} conjugate and gonadotropin suppression shows two distinct mechanisms of action in the treatment of adrenocortical tumors in transgenic mice expressing Simian Virus 40 T antigen under inhibin-{alpha} promoter Endocr. Relat. Cancer, June 1, 2009; 16(2): 549 - 564. [Abstract] [Full Text] [PDF]

				A. Makovitzki, A. Fink, and Y. Shai Suppression of Human Solid Tumor Growth in Mice by Intratumor and Systemic Inoculation of Histidine-Rich and pH-Dependent Host Defense-like Lytic Peptides Cancer Res., April 15, 2009; 69(8): 3458 - 3463. [Abstract] [Full Text] [PDF]

				A. Bjorstad, G. Askarieh, K. L. Brown, K. Christenson, H. Forsman, K. Onnheim, H.-N. Li, S. Teneberg, O. Maier, D. Hoekstra, et al. The Host Defense Peptide LL-37 Selectively Permeabilizes Apoptotic Leukocytes Antimicrob. Agents Chemother., March 1, 2009; 53(3): 1027 - 1038. [Abstract] [Full Text] [PDF]

				A. J. Mason, W. Moussaoui, T. Abdelrahman, A. Boukhari, P. Bertani, A. Marquette, P. Shooshtarizaheh, G. Moulay, N. Boehm, B. Guerold, et al. Structural Determinants of Antimicrobial and Antiplasmodial Activity and Selectivity in Histidine-rich Amphipathic Cationic Peptides J. Biol. Chem., January 2, 2009; 284(1): 119 - 133. [Abstract] [Full Text] [PDF]

				S. Vuorenoja, A. Rivero-Muller, A. J Ziecik, I. Huhtaniemi, J. Toppari, and N. A Rahman Targeted therapy for adrenocortical tumors in transgenic mice through their LH receptor by Hecate-human chorionic gonadotropin {beta} conjugate Endocr. Relat. Cancer, June 1, 2008; 15(2): 635 - 648. [Abstract] [Full Text] [PDF]

				A. Banerjee, J. Roychoudhury, and N. Ali Stearylamine-bearing cationic liposomes kill Leishmania parasites through surface exposed negatively charged phosphatidylserine J. Antimicrob. Chemother., January 1, 2008; 61(1): 103 - 110. [Abstract] [Full Text] [PDF]

				T. A. Luster, J. He, X. Huang, S. N. Maiti, A. J. Schroit, P. G. de Groot, and P. E. Thorpe Plasma Protein beta-2-Glycoprotein 1 Mediates Interaction between the Anti-tumor Monoclonal Antibody 3G4 and Anionic Phospholipids on Endothelial Cells J. Biol. Chem., October 6, 2006; 281(40): 29863 - 29871. [Abstract] [Full Text] [PDF]

				R. Bucki and P. A. Janmey Interaction of the Gelsolin-Derived Antibacterial PBP 10 Peptide with Lipid Bilayers and Cell Membranes. Antimicrob. Agents Chemother., September 1, 2006; 50(9): 2932 - 2940. [Abstract] [Full Text] [PDF]

				X. Huang, M. Bennett, and P. E. Thorpe A Monoclonal Antibody that Binds Anionic Phospholipids on Tumor Blood Vessels Enhances the Antitumor Effect of Docetaxel on Human Breast Tumors in Mice Cancer Res., May 15, 2005; 65(10): 4408 - 4416. [Abstract] [Full Text] [PDF]

				S. Ran, J. He, X. Huang, M. Soares, D. Scothorn, and P. E. Thorpe Antitumor Effects of a Monoclonal Antibody that Binds Anionic Phospholipids on the Surface of Tumor Blood Vessels in Mice Clin. Cancer Res., February 15, 2005; 11(4): 1551 - 1562. [Abstract] [Full Text] [PDF]

				V. E. Kagan, G. G. Borisenko, B. F. Serinkan, Y. Y. Tyurina, V. A. Tyurin, J. Jiang, S. X. Liu, A. A. Shvedova, J. P. Fabisiak, W. Uthaisang, et al. Appetizing rancidity of apoptotic cells for macrophages: oxidation, externalization, and recognition of phosphatidylserine Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L1 - L17. [Abstract] [Full Text] [PDF]

				V. A. Fadok, M. L. Warner, D. L. Bratton, and P. M. Henson CD36 Is Required for Phagocytosis of Apoptotic Cells by Human Macrophages That Use Either a Phosphatidylserine Receptor or the Vitronectin Receptor ({alpha}v{beta}3) J. Immunol., December 1, 1998; 161(11): 6250 - 6257. [Abstract] [Full Text] [PDF]

				E. Bevers, P. Comfurius, D. Dekkers, M. Harmsma, and R. Zwaal Review : Regulatory mechanisms of transmembrane phospholipid distributions and pathophysiological implications of transbilayer lipid scrambling Lupus, January 1, 1998; 7(2_suppl): S126 - S131. [Abstract] [PDF]

				R. F.A. Zwaal and A. J. Schroit Pathophysiologic Implications of Membrane Phospholipid Asymmetry in Blood Cells Blood, February 15, 1997; 89(4): 1121 - 1132. [Full Text] [PDF]

				T. Pomorski, P. Muller, B. Zimmermann, K. Burger, P. F. Devaux, and A. Herrmann Transbilayer movement of fluorescent and spin-labeled phospholipids in the plasma membrane of human fibroblasts: a quantitative approach J. Cell Sci., March 1, 1996; 109(3): 687 - 698. [Abstract] [PDF]

				M.R. Bennett, D.F. Gibson, S.M. Schwartz, and J.F. Tait Binding and Phagocytosis of Apoptotic Vascular Smooth Muscle Cells Is Mediated in Part by Exposure of Phosphatidylserine Circ. Res., December 1, 1995; 77(6): 1136 - 1142. [Abstract] [Full Text]