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01.01.2016 | Preclinical study

The TRAIL receptor agonist drozitumab targets basal B triple-negative breast cancer cells that express vimentin and Axl

verfasst von: Jennifer L. Dine, Ciara C. O’Sullivan, Donna Voeller, Yoshimi E. Greer, Kathryn J. Chavez, Catherine M. Conway, Sarah Sinclair, Brandon Stone, Laleh Amiri-Kordestani, Anand S. Merchant, Stephen M. Hewitt, Seth M. Steinberg, Sandra M. Swain, Stanley Lipkowitz

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2016

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Abstract

Previously, we found that GST-tagged tumor necrosis factor-related apoptosis inducing ligand preferentially killed triple-negative breast cancer (TNBC) cells with a mesenchymal phenotype by activating death receptor 5 (DR5). The purpose of this study was to explore the sensitivity of breast cancer cell lines to drozitumab, a clinically tested DR5-specific agonist; identify potential biomarkers of drozitumab-sensitive breast cancer cells; and determine if those biomarkers were present in tumors from patients with TNBC. We evaluated viability, caspase activity, and sub-G1 DNA content in drozitumab-treated breast cancer cell lines and we characterized expression of potential biomarkers by immunoblot. Expression levels of vimentin and Axl were then explored in 177 TNBC samples from a publically available cDNA microarray dataset and by immunohistochemistry (IHC) in tumor tissue samples obtained from 53 African-American women with TNBC. Drozitumab-induced apoptosis in mesenchymal TNBC cell lines but not in cell lines from other breast cancer subtypes. The drozitumab-sensitive TNBC cell lines expressed the mesenchymal markers vimentin and Axl. Vimentin and Axl mRNA and protein were expressed in a subset of human TNBC tumors. By IHC, ~15 % of TNBC tumors had vimentin and Axl expression in the top quartile for both. These findings indicate that drozitumab-sensitive mesenchymal TNBC cells express vimentin and Axl, which can be identified in a subset of human TNBC tumors. Thus, vimentin and Axl may be useful to identify TNBC patients who would be most likely to benefit from a DR5 agonist.

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Titel: The TRAIL receptor agonist drozitumab targets basal B triple-negative breast cancer cells that express vimentin and Axl
verfasst von: Jennifer L. Dine
Ciara C. O’Sullivan
Donna Voeller
Yoshimi E. Greer
Kathryn J. Chavez
Catherine M. Conway
Sarah Sinclair
Brandon Stone
Laleh Amiri-Kordestani
Anand S. Merchant
Stephen M. Hewitt
Seth M. Steinberg
Sandra M. Swain
Stanley Lipkowitz
Publikationsdatum: 01.01.2016
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2016
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3673-z

Springer Medizin

The TRAIL receptor agonist drozitumab targets basal B triple-negative breast cancer cells that express vimentin and Axl

Abstract

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Springer Medizin

Abstract

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