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01-06-2012 | Preclinical Study

Basal-like breast cancer stem cells are sensitive to anti-DR5 mediated cytotoxicity

Authors: Angelina I. Londoño-Joshi, Patsy G. Oliver, Yufeng Li, Choo Hyung Lee, Andres Forero-Torres, Albert F. LoBuglio, Donald J. Buchsbaum

Published in: Breast Cancer Research and Treatment | Issue 2/2012

Abstract

Breast cancer stem cells (BrCSC) are resistant to common therapeutic modalities including chemotherapy, radiation, and hormonal agents. They are thought to contribute to treatment resistance, relapse, and metastases. This study examines the effect of a monoclonal anti-DR5 antibody (TRA-8) and chemotherapy (adriamycin, taxol) on BrCSC populations from basal-like breast cancer cell lines. Doubly enriched BrCSC (CD44⁺, CD24⁻, ALDH⁺) cells were exposed to TRA-8 and control reagents and examined for cytotoxicity, caspase activation, tumorsphere formation and tumorigenicity. Doubly enriched BrCSC populations expressed cell surface DR5 and were sensitive to TRA-8 mediated cytotoxicity with induction of caspase 8 and 3 activation. TRA-8 at sub-nanomolar concentrations inhibited 2LMP and SUM159 BrCSC tumorsphere formation and was more than 50-fold more inhibitory than TRAIL or anti-DR4 at equimolar concentrations. Chemotherapy treatment of 2LMP and SUM159 cell lines resulted in a relative increase of BrCSC, whereas TRA-8 produced a decrease in the percentage of BrCSC. TRA-8 exposure to 2LMP and SUM159 BrCSC preparations produced significant inhibition of tumorigenicity. DR5 maybe a therapeutic target on the surface of basal-like BrCSC which is amenable to agonistic monoclonal anti-DR5 therapy.

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Title: Basal-like breast cancer stem cells are sensitive to anti-DR5 mediated cytotoxicity
Authors: Angelina I. Londoño-Joshi
Patsy G. Oliver
Yufeng Li
Choo Hyung Lee
Andres Forero-Torres
Albert F. LoBuglio
Donald J. Buchsbaum
Publication date: 01-06-2012
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-011-1763-0

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