Journal article
Upregulated interleukin-6 expression contributes to erlotinib resistance in head and neck squamous cell carcinoma
Molecular oncology, Vol.9(7), pp.1371-1383
08/2015
DOI: 10.1016/j.molonc.2015.03.008
PMCID: PMC4523436
PMID: 25888065
Abstract
Despite the role of epidermal growth factor receptor (EGFR) signaling in head and neck squamous cell carcinoma (HNSCC) development and progression, clinical trials involving EGFR tyrosine kinase inhibitors (TKIs) have yielded poor results in HNSCC patients. Mechanisms of acquired resistance to the EGFR TKI erlotinib was investigated by developing erlotinib-resistant HNSCC cell lines and comparing their gene expression profiles with their parental erlotinib-sensitive HNSCC cell lines using microarray analyses and subsequent pathway and network analyses. Erlotinib-resistant HNSCC cells displayed a significant upregulation in immune response and inflammatory pathways compared to parental cells. Interleukin-6 (IL-6) was one of thirteen genes that was significantly differentially expressed in all erlotinib-resistant HNSCC cell lines, which was validated using RT-PCR and ELISA. Blockade of IL-6 signaling using the IL-6 receptor antagonist tocilizumab, was able to overcome erlotinib-resistance in erlotinib-resistant SQ20B tumors in vivo. Overall, erlotinib-resistant HNSCC cells display elevated IL-6 expression levels compared to erlotinib-sensitive HNSCC cells and blockade of the IL-6 signaling pathway may be an effective strategy to overcome resistance to erlotinib and possibly other EGFR TKIs for HNSCC therapy.
•Inflammatory pathways and processes were upregulated in erlotinib-resistant HNSCC cells.•Networks involving MyD88-dependent TLR signaling were identified in erlotinib-resistant HNSCC cells.•IL-6 expression and secretion was increased in erlotinib-resistant HNSCC cells.•Blockade of IL-6 signaling overcame erlotinib resistance.
Details
- Title: Subtitle
- Upregulated interleukin-6 expression contributes to erlotinib resistance in head and neck squamous cell carcinoma
- Creators
- Aditya Stanam - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USALaurie Love-Homan - Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IA, USATisha S Joseph - Lincoln University of the Commonwealth of Pennsylvania, Lincoln, PA, USAMadelyn Espinosa-Cotton - Department of Pathology, Carver College of Medicine, The University of Iowa, Iowa City, IA, USAAndrean L Simons - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Molecular oncology, Vol.9(7), pp.1371-1383
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.molonc.2015.03.008
- PMID
- 25888065
- PMCID
- PMC4523436
- ISSN
- 1574-7891
- eISSN
- 1878-0261
- Language
- English
- Date published
- 08/2015
- Academic Unit
- Oral Pathology, Radiology and Medicine; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology
- Record Identifier
- 9984047658802771
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