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CD20-induced lymphoma cell death is independent of both caspases and its redistribution into Triton X-100 insoluble membrane rafts

CD20-induced lymphoma cell death is independent of both caspases and its redistribution into Triton X-100 insoluble membrane rafts
CD20-induced lymphoma cell death is independent of both caspases and its redistribution into Triton X-100 insoluble membrane rafts
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.
0008-5472
5480-5489
Chan, H.T. Claude
b109c93f-7e9a-44ee-ad12-da757b1b11fc
Hughes, David
e282c0b9-a459-457f-8d66-bfa224e63266
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Tutt, Alison L.
46ce577b-aea1-412d-84ea-fc4dab794469
Walshe, Claire A.
dc2839de-0958-478e-a3fe-e7ed361fcda2
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Chan, H.T. Claude
b109c93f-7e9a-44ee-ad12-da757b1b11fc
Hughes, David
e282c0b9-a459-457f-8d66-bfa224e63266
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Tutt, Alison L.
46ce577b-aea1-412d-84ea-fc4dab794469
Walshe, Claire A.
dc2839de-0958-478e-a3fe-e7ed361fcda2
Teeling, Jessica L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Glennie, Martin J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c

Chan, H.T. Claude, Hughes, David, French, Ruth R., Tutt, Alison L., Walshe, Claire A., Teeling, Jessica L., Glennie, Martin J. and Cragg, Mark S. (2003) CD20-induced lymphoma cell death is independent of both caspases and its redistribution into Triton X-100 insoluble membrane rafts. Cancer Research, 63 (17), 5480-5489.

Record type: Article

Abstract

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.

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Published date: 1 September 2003

Identifiers

Local EPrints ID: 26240
URI: http://eprints.soton.ac.uk/id/eprint/26240
ISSN: 0008-5472
PURE UUID: 2dfe4eda-fdaf-4e42-a5c8-446e2b2aa817
ORCID for H.T. Claude Chan: ORCID iD orcid.org/0000-0003-0530-9480
ORCID for Jessica L. Teeling: ORCID iD orcid.org/0000-0003-4004-7391
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

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Date deposited: 24 Apr 2006
Last modified: 23 Jul 2022 01:53

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Contributors

Author: H.T. Claude Chan ORCID iD
Author: David Hughes
Author: Ruth R. French
Author: Alison L. Tutt
Author: Claire A. Walshe
Author: Mark S. Cragg ORCID iD

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