Dual “mAb” HER family blockade in head and neck cancer human cell lines combined with photon therapy
Abstract Head and neck cancer stem cells (CSCs) are highly resistant to treatment. When EGFR is overexpressed in head and neck squamous cell carcinoma (HNSCC), HER2 and HER3 are also expressed. The aim of the present study was to investigate the effect of HER1/2/3 blockade through a combination of c...
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Nature Portfolio
2017
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oai:doaj.org-article:25541696948a416d88c4361dcc1a37472021-12-02T11:53:10ZDual “mAb” HER family blockade in head and neck cancer human cell lines combined with photon therapy10.1038/s41598-017-12367-72045-2322https://doaj.org/article/25541696948a416d88c4361dcc1a37472017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-12367-7https://doaj.org/toc/2045-2322Abstract Head and neck cancer stem cells (CSCs) are highly resistant to treatment. When EGFR is overexpressed in head and neck squamous cell carcinoma (HNSCC), HER2 and HER3 are also expressed. The aim of the present study was to investigate the effect of HER1/2/3 blockade through a combination of cetuximab and pertuzumab, with or without photon irradiation, on the proliferation and migration/invasion capabilities of an HNSCC chemo- and radioresistant human cell line (SQ20B) and its corresponding stem cell subpopulation. Cell proliferation, migration and invasion were studied after treatment with cetuximab +/− pertuzumab +/− 10 Gy photon irradiation. EGFR, phospho-EGFR, HER2 and HER3 protein expression levels were studied. Activation or inhibition of the RAS/MAPK and AKT-mTOR downstream signalling cascades was investigated through phospho-AKT and phospho-MEK1/2 expression. Cetuximab strongly inhibited SQ20B and FaDu cell proliferation, migration and invasion, whereas it had little effect on SQ20B-CSCs. Cetuximab–pertuzumab combined with radiation significantly inhibited SQ20B and FaDu cell and SQ20B-CSC proliferation, migration and invasion. Cetuximab–pertuzumab with 10 Gy photon irradiation switched off both phospho-AKT and phospho-MEK1/2 expression in the three populations. The triple therapy is therefore thought to inhibit SQ20B cells, SQ20B-CSCs and FaDu cells through an AKT-mTOR and Ras-MAPK downstream signalling blockade.Jean-Baptiste GuyBenoîte MéryEdouard OllierSophie EspenelAlexis VallardAnne-Sophie WoznyStéphanie SimonetAlexandra LauretPriscillia Battiston-MontagneDominique ArdailGersende AlphonseChloé RancouleClaire Rodriguez-LafrasseNicolas MagnéNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Jean-Baptiste Guy Benoîte Méry Edouard Ollier Sophie Espenel Alexis Vallard Anne-Sophie Wozny Stéphanie Simonet Alexandra Lauret Priscillia Battiston-Montagne Dominique Ardail Gersende Alphonse Chloé Rancoule Claire Rodriguez-Lafrasse Nicolas Magné Dual “mAb” HER family blockade in head and neck cancer human cell lines combined with photon therapy |
| description |
Abstract Head and neck cancer stem cells (CSCs) are highly resistant to treatment. When EGFR is overexpressed in head and neck squamous cell carcinoma (HNSCC), HER2 and HER3 are also expressed. The aim of the present study was to investigate the effect of HER1/2/3 blockade through a combination of cetuximab and pertuzumab, with or without photon irradiation, on the proliferation and migration/invasion capabilities of an HNSCC chemo- and radioresistant human cell line (SQ20B) and its corresponding stem cell subpopulation. Cell proliferation, migration and invasion were studied after treatment with cetuximab +/− pertuzumab +/− 10 Gy photon irradiation. EGFR, phospho-EGFR, HER2 and HER3 protein expression levels were studied. Activation or inhibition of the RAS/MAPK and AKT-mTOR downstream signalling cascades was investigated through phospho-AKT and phospho-MEK1/2 expression. Cetuximab strongly inhibited SQ20B and FaDu cell proliferation, migration and invasion, whereas it had little effect on SQ20B-CSCs. Cetuximab–pertuzumab combined with radiation significantly inhibited SQ20B and FaDu cell and SQ20B-CSC proliferation, migration and invasion. Cetuximab–pertuzumab with 10 Gy photon irradiation switched off both phospho-AKT and phospho-MEK1/2 expression in the three populations. The triple therapy is therefore thought to inhibit SQ20B cells, SQ20B-CSCs and FaDu cells through an AKT-mTOR and Ras-MAPK downstream signalling blockade. |
| format |
article |
| author |
Jean-Baptiste Guy Benoîte Méry Edouard Ollier Sophie Espenel Alexis Vallard Anne-Sophie Wozny Stéphanie Simonet Alexandra Lauret Priscillia Battiston-Montagne Dominique Ardail Gersende Alphonse Chloé Rancoule Claire Rodriguez-Lafrasse Nicolas Magné |
| author_facet |
Jean-Baptiste Guy Benoîte Méry Edouard Ollier Sophie Espenel Alexis Vallard Anne-Sophie Wozny Stéphanie Simonet Alexandra Lauret Priscillia Battiston-Montagne Dominique Ardail Gersende Alphonse Chloé Rancoule Claire Rodriguez-Lafrasse Nicolas Magné |
| author_sort |
Jean-Baptiste Guy |
| title |
Dual “mAb” HER family blockade in head and neck cancer human cell lines combined with photon therapy |
| title_short |
Dual “mAb” HER family blockade in head and neck cancer human cell lines combined with photon therapy |
| title_full |
Dual “mAb” HER family blockade in head and neck cancer human cell lines combined with photon therapy |
| title_fullStr |
Dual “mAb” HER family blockade in head and neck cancer human cell lines combined with photon therapy |
| title_full_unstemmed |
Dual “mAb” HER family blockade in head and neck cancer human cell lines combined with photon therapy |
| title_sort |
dual “mab” her family blockade in head and neck cancer human cell lines combined with photon therapy |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/25541696948a416d88c4361dcc1a3747 |
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