This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Chan, H. T. C. Articles by Cragg, M. S. Search for Related Content PubMed PubMed Citation Articles by Chan, H. T. C. Articles by Cragg, M. S.

CD20-induced Lymphoma Cell Death Is Independent of Both Caspases and Its Redistribution into Triton X-100 Insoluble Membrane Rafts¹

Tenovus Research Laboratory, Cancer Sciences Division, School of Medicine, General Hospital, Tremona Road, Southampton, SO16 6YD United Kingdom [H. T. C., D. H., R. R. F., A. L. T., C. A. W., M. J. G., M. S. C.], and Genmab, Utrecht, the Netherlands [J. L. T.]

Rituximab is routinely used for the treatment of neoplasia, although the mechanism of action remains uncertain. In the current study, CD20-induced apoptosis was investigated with a panel of anti-CD20 monoclonal antibodies (mAb) in a wide range of cell lines. A hierarchy of mAb activity was apparent, with the B1 mAb generally the most potent. Apoptosis through CD20 was dependent on the nature of mAb binding and correlated with the extent of homotypic cell adhesion induced. However, using anti-CD20 mAb, which vary in the extent to which they redistribute wild-type and mutant CD20 molecules to membrane rafts, we showed that CD20-induced apoptosis was independent of translocation to TX-100 insoluble rafts. Using crmA-transfected cells and caspase inhibitors, we showed that phosphatidylserine translocation and mitochondrial permeability transition evoked during CD20-induced apoptosis appeared caspase independent. Furthermore, in cytoplasts which lack mitochondria and in Bcl₂-transfected cells, phosphatidylserine was still translocated to the cell surface after CD20 stimulation. Together, these data imply that CD20 can evoke apoptosis without the involvement of mitochondria and caspases and irrespective of redistribution into TX-100 insoluble membrane rafts.

This article has been cited by other articles:

				B. Li, S. Shi, W. Qian, L. Zhao, D. Zhang, S. Hou, L. Zheng, J. Dai, J. Zhao, H. Wang, et al. Development of Novel Tetravalent Anti-CD20 Antibodies with Potent Antitumor Activity Cancer Res., April 1, 2008; 68(7): 2400 - 2408. [Abstract] [Full Text] [PDF]

				J. Du, H. Wang, C. Zhong, B. Peng, M. Zhang, B. Li, S. Huo, Y. Guo, and J. Ding Structural Basis for Recognition of CD20 by Therapeutic Antibody Rituximab J. Biol. Chem., May 18, 2007; 282(20): 15073 - 15080. [Abstract] [Full Text] [PDF]

				J. L. Teeling, W. J. M. Mackus, L. J. J. M. Wiegman, J. H. N. van den Brakel, S. A. Beers, R. R. French, T. van Meerten, S. Ebeling, T. Vink, J. W. Slootstra, et al. The Biological Activity of Human CD20 Monoclonal Antibodies Is Linked to Unique Epitopes on CD20 J. Immunol., July 1, 2006; 177(1): 362 - 371. [Abstract] [Full Text] [PDF]

				F. Perosa, E. Favoino, M. A. Caragnano, and F. Dammacco Generation of biologically active linear and cyclic peptides has revealed a unique fine specificity of rituximab and its possible cross-reactivity with acid sphingomyelinase-like phosphodiesterase 3b precursor Blood, February 1, 2006; 107(3): 1070 - 1077. [Abstract] [Full Text] [PDF]

				Z. Gu, J. Yamashiro, E. Kono, and R. E. Reiter Anti-Prostate Stem Cell Antigen Monoclonal Antibody 1G8 Induces Cell Death In vitro and Inhibits Tumor Growth In vivo via a Fc-Independent Mechanism Cancer Res., October 15, 2005; 65(20): 9495 - 9500. [Abstract] [Full Text] [PDF]

				N. Zhang, L. A. Khawli, P. Hu, and A. L. Epstein Generation of Rituximab Polymer May Cause Hyper-Cross-linking-Induced Apoptosis in Non-Hodgkin's Lymphomas Clin. Cancer Res., August 15, 2005; 11(16): 5971 - 5980. [Abstract] [Full Text] [PDF]

				A. R. Jazirehi, S. Huerta-Yepez, G. Cheng, and B. Bonavida Rituximab (Chimeric Anti-CD20 Monoclonal Antibody) Inhibits the Constitutive Nuclear Factor-{kappa}B Signaling Pathway in Non-Hodgkin's Lymphoma B-Cell Lines: Role in Sensitization to Chemotherapeutic Drug-induced Apoptosis Cancer Res., January 1, 2005; 65(1): 264 - 276. [Abstract] [Full Text] [PDF]

				R. L. Wahl Tositumomab and 131I Therapy in Non-Hodgkin's Lymphoma J. Nucl. Med., January 1, 2005; 46(1_suppl): 128S - 140S. [Abstract] [Full Text] [PDF]

				G. Cartron, H. Watier, J. Golay, and P. Solal-Celigny From the bench to the bedside: ways to improve rituximab efficacy Blood, November 1, 2004; 104(9): 2635 - 2642. [Abstract] [Full Text] [PDF]

				A. R. Jazirehi, M. I. Vega, D. Chatterjee, L. Goodglick, and B. Bonavida Inhibition of the Raf-MEK1/2-ERK1/2 Signaling Pathway, Bcl-xL Down-Regulation, and Chemosensitization of Non-Hodgkin's Lymphoma B Cells by Rituximab Cancer Res., October 1, 2004; 64(19): 7117 - 7126. [Abstract] [Full Text] [PDF]

				J. L. Teeling, R. R. French, M. S. Cragg, J. van den Brakel, M. Pluyter, H. Huang, C. Chan, P. W. H. I. Parren, C. E. Hack, M. Dechant, et al. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas Blood, September 15, 2004; 104(6): 1793 - 1800. [Abstract] [Full Text] [PDF]

				C. Bezombes, S. Grazide, C. Garret, C. Fabre, A. Quillet-Mary, S. Muller, J.-P. Jaffrezou, and G. Laurent Rituximab antiproliferative effect in B-lymphoma cells is associated with acid-sphingomyelinase activation in raft microdomains Blood, August 15, 2004; 104(4): 1166 - 1173. [Abstract] [Full Text] [PDF]

				A. J. Olszewski and M. L. Grossbard Empowering Targeted Therapy: Lessons from Rituximab Sci. Signal., July 13, 2004; 2004(241): pe30 - pe30. [Abstract] [Full Text] [PDF]

				R. Stein, Z. Qu, S. Chen, A. Rosario, V. Shi, M. Hayes, I. D. Horak, H. J. Hansen, and D. M. Goldenberg Characterization of a New Humanized Anti-CD20 Monoclonal Antibody, IMMU-106, and Its Use in Combination with the Humanized Anti-CD22 Antibody, Epratuzumab, for the Therapy of Non-Hodgkin's Lymphoma Clin. Cancer Res., April 15, 2004; 10(8): 2868 - 2878. [Abstract] [Full Text] [PDF]

				M. S. Cragg and M. J. Glennie Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents Blood, April 1, 2004; 103(7): 2738 - 2743. [Abstract] [Full Text] [PDF]