A sequence-specific DNA binding small molecule triggers the release of immunogenic signals and phagocytosis in a model of B-cell lymphoma

Quarterly Reviews of Biophysics - Tập 48 Số 4 - Trang 453-464 - 2015
JeenJoo S. Kang1, Peter B. Dervan1
1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena CA 91125 USA

Tóm tắt

AbstractMeans to cause an immunogenic cell death could lead to significant insight into how cancer escapes immune control. In this study, we screened a library of five pyrrole–imidazole polyamides coding for different DNA sequences in a model of B-cell lymphoma for the upregulation of surface calreticulin, a pro-phagocytosis signal implicated in immunogenic cell death. We found that hairpin polyamide 1 triggers the release of the damage-associated molecular patterns calreticulin, ATP and HMGB1 in a slow necrotic-type cell death. Consistent with this signaling, we observed an increase in the rate of phagocytosis by macrophages after the cancer cells were exposed to polyamide 1. The DNA sequence preference of polyamide 1 is 5′-WGGGTW-3′ (where W = A/T), indicated by the pairing rules and confirmed by the Bind-n-Seq method. The close correspondence of this sequence with the telomere-repeat sequence suggests a potential mechanism of action through ligand binding at the telomere. This study reveals a chemical means to trigger an inflammatory necrotic cell death in cancer cells.

Từ khóa


Tài liệu tham khảo

10.1126/scitranslmed.3001375

10.1016/S1074-5521(97)90243-X

10.1146/annurev.immunol.22.012703.104803

10.1038/sj.embor.7400205

10.1073/pnas.1118506109

10.1016/j.it.2007.08.004

10.1038/sj.cdd.4402275

10.1073/pnas.1305569110

10.1038/nsb0298-104

10.1021/ja00097a004

10.1126/science.282.5386.111

10.4161/onci.27560

10.1021/ol3010003

10.1042/BJ20081847

10.1038/nature06309

10.1016/S0959-440X(03)00081-2

10.1038/36116

10.1158/0008-5472.CAN-09-3566

10.1016/j.immuni.2013.02.003

10.1016/j.tet.2007.03.041

Schreiber, 2011, Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion, Science Signalling, 331, 1565

10.1038/emboj.2009.1

10.1038/382559a0

10.1021/ja00049a006

10.1093/emboj/20.12.3218

10.1021/cb700110z

10.1158/1535-7163.MCT-12-1040

10.1021/ja308888c

10.1182/blood.V100.3.925

10.1021/ja960720z

10.1016/j.it.2010.04.001

10.1038/nm1523

10.1084/jem.20112738

10.1016/0092-8674(89)90685-5

10.1038/nri2216

10.1126/science.1071059

10.1021/ja500211z

10.1016/j.immuni.2004.07.017

10.1021/ja406737n

10.1073/pnas.0704217104

10.1038/nature03884

10.4049/jimmunol.1003267

10.1073/pnas.1222035110

10.1007/s10555-011-9273-4

10.1016/j.cell.2011.02.013

10.1021/ja9611598

10.1073/pnas.93.16.8306

10.1016/j.cell.2010.02.015

10.4049/jimmunol.1100690

10.1093/nar/gku866

Thông tin
Thông tin xuất bản

Quarterly Reviews of Biophysics

Tập 48 Số 4

453-464

Thông tin tác giả