This Article Full Text 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 Chen, S. Articles by Tomlinson, S. Search for Related Content PubMed PubMed Citation Articles by Chen, S. Articles by Tomlinson, S.

CD59 Expressed on a Tumor Cell Surface Modulates Decay-accelerating Factor Expression and Enhances Tumor Growth in a Rat Model of Human Neuroblastoma¹

Department of Pathology, New York University School of Medicine, New York, New York 10016 [S. C., T. C., S. T.], and Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [N-K. V. C.]

It has been hypothesized that complement inhibitors expressed on the surface of tumor cells prevent effective immune-mediated clearance. Whereas there are in vitro data to support this hypothesis, the species-selective activity of complement inhibitors has been a hindrance to investigating the role of membrane-bound complement inhibitors in rodent models of human cancer. The CD59-positive LAN-1 human neuroblastoma cell line was significantly more sensitive to lysis by rat complement than by human complement, illustrating the species selectivity of endogenously expressed complement inhibitors. Transfection of LAN-1 cells with rat CD59, an inhibitor of the terminal cytolytic membrane attack complex, effectively protected the cells from lysis by rat complement in vitro. When LAN-1 cells stably expressing rat CD59 were inoculated into immune-deficient rats, the onset of tumor growth and the rate of tumor growth were significantly enhanced compared with those of control-transfected LAN-1 cells. These data show directly that the expression of a complement inhibitor on a tumor cell promotes tumor growth. Flow cytometric analysis revealed that the endogenous expression of decay-accelerating factor (DAF), an inhibitor of complement activation, was up-regulated on the surface of cells after in vivo growth. Of further interest, higher levels of DAF were present on CD59-transfected cells than on control-transfected cells derived from tumors. Increased DAF expression correlated with decreased complement deposition on the tumor cell surface. These results show that expression of complement inhibitors on a tumor cell has functional consequences with regard to complement deposition in vivo and indicate that CD59 can indirectly effect complement activation and C3 deposition in vivo via a link between CD59 and DAF expression.

This article has been cited by other articles:

				S. M. Mangsbo, J. Sanchez, K. Anger, J. D. Lambris, K. N. Ekdahl, A. S. Loskog, B. Nilsson, and T. H. Totterman Complement Activation by CpG in a Human Whole Blood Loop System: Mechanisms and Immunomodulatory Effects J. Immunol., November 15, 2009; 183(10): 6724 - 6732. [Abstract] [Full Text] [PDF]

				R. M. Donev, L. C. Gray, B. Sivasankar, T. R. Hughes, C. W. van den Berg, and B. P. Morgan Modulation of CD59 Expression by Restrictive Silencer Factor-Derived Peptides in Cancer Immunotherapy for Neuroblastoma Cancer Res., July 15, 2008; 68(14): 5979 - 5987. [Abstract] [Full Text] [PDF]

				M. Imai, R. Ohta, J. C. Varela, H. Song, and S. Tomlinson Enhancement of Antibody-Dependent Mechanisms of Tumor Cell Lysis by a Targeted Activator of Complement Cancer Res., October 1, 2007; 67(19): 9535 - 9541. [Abstract] [Full Text] [PDF]

				Y. Huang, C. A. Smith, H. Song, B. P. Morgan, R. Abagyan, and S. Tomlinson Insights into the Human CD59 Complement Binding Interface Toward Engineering New Therapeutics J. Biol. Chem., October 7, 2005; 280(40): 34073 - 34079. [Abstract] [Full Text] [PDF]

				R. Ohta, N. Kondor, N. Dohi, S. Tomlinson, M. Imai, V. M. Holers, H. Okada, and N. Okada Mouse Complement Receptor-Related Gene y/p65-Neutralized Tumor Vaccine Induces Antitumor Activity In Vivo J. Immunol., July 1, 2004; 173(1): 205 - 213. [Abstract] [Full Text] [PDF]

				M. Zatyka, N. F. da Silva, S. C. Clifford, M. R. Morris, M. S. Wiesener, K.-U. Eckardt, R. S. Houlston, F. M. Richards, F. Latif, and E. R. Maher Identification of Cyclin D1 and Other Novel Targets for the von Hippel-Lindau Tumor Suppressor Gene by Expression Array Analysis and Investigation of Cyclin D1 Genotype as a Modifier in von Hippel-Lindau Disease Cancer Res., July 1, 2002; 62(13): 3803 - 3811. [Abstract] [Full Text] [PDF]

				T. A. Caragine, N. Okada, A. B. Frey, and S. Tomlinson A Tumor-expressed Inhibitor of the Early but not Late Complement Lytic Pathway Enhances Tumor Growth in a Rat Model of Human Breast Cancer Cancer Res., February 1, 2002; 62(4): 1110 - 1115. [Abstract] [Full Text] [PDF]