Oncotarget

Research Papers:

Effects of Cetuximab and Erlotinib on the behaviour of cancer stem cells in head and neck squamous cell carcinoma

Maria Fernanda Setúbal Destro Rodrigues, Luke Gammon, Muhammad M. Rahman, Adrian Biddle, Fabio Daumas Nunes and Ian C. Mackenzie _

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Oncotarget. 2018; 9:13488-13500. https://doi.org/10.18632/oncotarget.24416

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Abstract

Maria Fernanda Setúbal Destro Rodrigues1, Luke Gammon2, Muhammad M. Rahman2, Adrian Biddle2, Fabio Daumas Nunes1 and Ian C. Mackenzie2

1Oral Pathology Department, School of Dentistry, University of São Paulo, São Paulo, Brazil

2Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

Correspondence to:

Ian C. Mackenzie, email: i.c.mackenzie@qmul.ac.uk

Keywords: HNSCC; cancer stem cells; Cetuximab; EMT; differentiation

Received: April 28, 2017     Accepted: January 20, 2018     Published: February 05, 2018

ABSTRACT

The therapeutic responses of many solid tumours to chemo- and radio-therapies are far from fully effective but therapies targeting malignancy-related cellular changes show promise for further control. In head and neck squamous cell carcinoma, the epidermal growth factor receptor (EGFR) is commonly overexpressed and investigation of agents that block this receptor indicate a limited response when used alone but an ability to enhance the actions of other drugs. The hierarchical stem cell patterns present in tumours generate cellular heterogeneity and this is further complicated by cancer stem cells (CSC) shifting between epithelial (Epi-CSC) and mesenchymal (EMT-CSC) states. To clarify how such heterogeneity influences responses to EGFR blocking, we examined the effects of Cetuximab and Erlotinib on the cell sub-populations in HNSCC cell lines. These agents reduced cell proliferation for all subpopulations but induced little cell death. They did however induce large shifts of cells between the EMT-CSC, Epi-CSC and differentiating cell compartments. Loss of EMT-CSCs reduced cell motility and is expected to reduce invasion and metastasis. EGFR blocking also induced shifts of Epi-CSCs into the differentiating cell compartment which typically has greater sensitivity to chemo/radiation, an effect expected to enhance the overall response of tumour cell populations to adjunctive therapies.


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