Differential escape mechanisms in cetuximab-resistant head and neck cancer cells.

Autor: Willey CD; Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35249, USA., Anderson JC; Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35249, USA., Trummell HQ; Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35249, USA., Naji F; PamGene International, 's-Hertogenbosch, the Netherlands., de Wijn R; PamGene International, 's-Hertogenbosch, the Netherlands., Yang ES; Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35249, USA., Bredel M; Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35249, USA., Thudi NK; Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35249, USA., Bonner JA; Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35249, USA. Electronic address: gesims@uabmc.edu.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2019 Sep 10; Vol. 517 (1), pp. 36-42. Date of Electronic Publication: 2019 Jul 13.
DOI: 10.1016/j.bbrc.2019.06.159
Abstrakt: Acquired cetuximab resistance is a challenge for oncologists treating advanced head and neck carcinoma (HNC). While intrinsic cetuximab resistance mechanism in colorectal cancer is known, resistance in HNC is unclear. We established two different cetuximab resistant HNC cell lines by culturing epidermal growth factor (EGFR) expressing UM-SCC-1 and UM-SCC-6 cell lines in the presence of 5 μg/ml cetuximab. We then explored potential mechanisms of resistance. We found that the 2 cell lines developed resistance by different mechanisms. Specifically, we found that UM-SCC-1 resistant cells (UM-SCC-1R) showed enhanced EGF-induced downstream signals while UM-SCC-6 resistant cells (UM-SCC-6R) demonstrated EGF-independent signaling. Global kinase activity (kinomic) profiling revealed unique signaling differences in the two resistant cell lines. However, both of the resistant lines demonstrated increased phospho-serine 727 and total STAT3 expression compared to the parental lines. STAT3 knockdown promoted increased cytotoxicity both in the presence and absence of cetuximab in the resistant lines suggesting that STAT3 may be a common target in cetuximab resistance.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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